Health

Exercise is Medicine: How Moving Your Body Calms Your Mind

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Abstract created by G. Sparks

Memories play a huge role in our everyday lives. We’re constantly forming them, whether we realize it or not, and they help us navigate the world around us. Built from our experiences and environments, memories allow us to adapt, grow, and prepare for similar situations in the future.1 But not all memories are created equal. Our brains tend to hold onto stressful or traumatic events more strongly, creating lasting imprints that can shape how we think and feel. Over time, these intense memories can contribute to the development of anxiety in certain situations. In more severe cases, they may even lead to conditions like post-traumatic stress disorder (PTSD).

PTSD can seriously impact a person’s quality of life, often bringing nightmares, flashbacks, negative thought patterns, mood swings, and other overwhelming symptoms.1 Many people coping with PTSD or chronic anxiety turn to therapy or medication for relief and those treatments can be incredibly helpful. But what if there were also a natural way to help ease those symptoms? What if something as simple as movement, like exercise that could play a role in healing the brain?

Recent research has been exploring exactly that. Studies show that exercise can act as a form of medicine, helping the brain and body gradually shift out of survival mode and into a healthier, more balanced state.

Understanding the Science Behind Anxiety

When it comes to the science of anxiety, researchers have proposed many pathways to explain how stress impacts the brain. One particularly interesting pathway involves gene transcription and how it contributes to the consolidation of event-associated memories, especially those tied to stressful or traumatic experiences.1

Two key players in this process are corticosterone (a stress hormone) and glutamate (a neurotransmitter). During a stressful event, these molecules work together to set off a cascade of biological events that ultimately encode the memory of that event into long-term storage.

Here’s how it happens: Glutamate binds to NMDA receptors located on dentate gyrus granule neurons in the hippocampus. This binding allows calcium ions to flow into the cell, initiating a signaling pathway that activates MEK, which in turn activates ERK through phosphorylation. ERK then travels into the nucleus of the neuron.

At the same time, corticosterone enters the cell and binds to glucocorticoid receptors (GR), which also move into the nucleus. Once inside, ERK and GR interact, allowing pERK1/2 to phosphorylate two important molecules: MSK1/2 and Elk-1. These molecules then go on to modify the H3 histone by phosphorylating and acetylating it.

This modification causes the chromatin, which was previously tightly wound around the histones and inaccessible, to loosen. This unwinding opens up the DNA, allowing gene transcription to occur. The result is the consolidation of the memory associated with that stressful event.

A visual representation of this pathway is shown in Figure 1 below. For a more detailed explanation of the molecular cascade and its components, refer to the full article.

 

Figure 1. A diagram that illustrates the pathway of corticosterone and glutamate signaling leading to the consolidation of event associated memories. 1

Exercise and Its Role in Reducing Stress and Anxiety

Traditionally, medication and therapy have been the two primary treatments for individuals dealing with anxiety. While both can be highly effective, medications sometimes come with side effects or interactions, especially for people managing other conditions like ADHD.1 In recent years, however, there’s been a growing interest in the therapeutic potential of exercise as a powerful, natural intervention for anxiety.

Research has shown that regular aerobic exercise can reduce the reactivity of both the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis which are two key systems involved in the body’s stress response.2 The HPA axis plays a central role in regulating cortisol levels, and exercise has been found to induce long-term adaptations that help moderate stress reactivity and reduce anxiety symptoms.

Exercise also influences several important neurotransmitter systems. In animal studies, physical activity has been linked to increased levels of monoamines such as serotonin, dopamine, and norepinephrine which are chemicals that are commonly targeted by antidepressant medications.2 These changes can produce an antidepressant-like effect and help improve mood stability.

Another important system affected by exercise is the opioid system. Physical activity triggers the release of beta-endorphins, which are natural painkillers and mood enhancers.2 This release is believed to contribute to the well-known “runner’s high” and can significantly lower perceived levels of stress and anxiety.

Additionally, exercise has been shown to increase levels of brain-derived neurotrophic factor (BDNF) which is a key neurotrophin that supports the growth and resilience of neurons.2 Elevated BDNF levels are associated with better emotional regulation, enhanced cognitive function, and improved mental health outcomes.

Together, these biological effects suggest that exercise doesn’t just distract from anxiety, but that it may actually reshape the brain’s response to stress in a meaningful and lasting way.

Here is another link to an article that takes an in depth look on the effects of exercise and physical activity on anxiety.

Final Thoughts

Anxiety is a complex condition that’s closely tied to how our brain stores and responds to stressful events. In some cases, these memories are helpful since they prepare us to react and adapt when similar situations arise in the future. But when the stress is too intense or traumatic, those memories can become harmful. In some individuals, this can lead to the development of PTSD, a condition that often reduces quality of life through persistent fear, anxiety, and emotional distress.

While medications and therapy are effective for many people, they aren’t perfect solutions and can come with complications or limitations. Fortunately, a growing body of research points to exercise as a promising complementary approach. Though it can’t erase trauma, regular physical activity may be a reliable and accessible way to improve mood and reduce the physical and emotional burden of stress.

Whether it’s going for a walk, lifting weights, movement has the power to heal. Exercise truly is a form of medicine, and it might just be one of the most effective tools we have for supporting mental health.

References

(1)      Reul, J. M. H. M. Making Memories of Stressful Events: A Journey along Epigenetic, Gene Transcription, and Signaling Pathways. Frontiers in Psychiatry. 2014. https://doi.org/10.3389/fpsyt.2014.00005.

(2)      Anderson, E.; Shivakumar, G. Effects of Exercise and Physical Activity on Anxiety. Front Psychiatry 2013, 4 (APR). https://doi.org/10.3389/fpsyt.2013.00027.

 

Community/Health

Addiction Rewires Your Brain: Can We Rewire It Back?

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Artstract created S. Mohamed

Addiction is not a choice. It’s a complex brain disease. And for millions of people struggling with psychostimulant use—cocaine, meth, nicotine, and amphetamines—it can feel like there’s no way out. While we know these drugs hijack the brain’s reward system, we’re still uncovering how they reshape it at the molecular level. Until now, there hasn’t been a strong therapeutic target to reverse these brain changes and truly help people recover. But new research offers a powerful insight: a group of brain receptors called metabotropic glutamate receptors (mGluRs) might be the key to healing the brain after drug abuse.

Therefore, understanding how these receptors work could change the way we treat—and talk about—addiction. Let’s unpack how psychostimulants mess with our brain chemistry and why that makes addiction less of a choice and more of a brain health issue.

The Reward Circuit and Dopamine: Why Drugs Feel Good

Dopamine is the brain’s “feel-good” chemical. It spikes when you experience something pleasurable like eating chocolate, getting a compliment, scrolling TikTok at 1 a.m. It also spikes when someone uses a drug. And that’s where the problem starts.

Dopamine plays a huge role in the brain’s reward system, which includes areas like the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC). When dopamine floods this system, the brain takes note: “This felt good. Let’s do it again.” Over time, your brain builds tolerance, needing more and more of the drug just to feel normal.

But there’s another layer: the brain learns to expect dopamine in certain contexts maybe it’s a particular room, a group of friends, or even a certain time of day. These environmental triggers can increase tolerance or make someone more likely to relapse. And when the drug is taken outside of that context, the body isn’t ready leading to accidental overdose[2].

Figure[1]. This figure illustrates the brain’s reward circuit connecting the prefrontal cortex, nucleus accumbens, and ventral tegmental area via dopamine signaling and how its dysregulation contributes to addiction.

Glutamate: Reinforcing the Habit

While dopamine makes drugs feel good, glutamate helps the brain remember how good it felt.

Glutamate is the brain’s main excitatory neurotransmitter. It’s essential for learning, memory, and synaptic plasticity a fancy term for how the brain strengthens or weakens connections between neurons. Drugs like cocaine, nicotine, and amphetamine increase glutamate levels and hijack these learning processes.

They do this by activating metabotropic glutamate receptors (mGluRs)—especially Group I receptors like mGluR1 and mGluR5. These receptors become overexpressed or relocated to different parts of neurons. For example, mGluR5 increases in the prefrontal cortex, while mGluR1 spreads into extrasynaptic sites, both changes linked to long-term neuroplasticity in addiction[1].

The result? The brain gets really good at learning how to crave drugs and not so great at resisting them.

Figure [2].  Brain regions and synaptic pathways involved in addiction, showing how Group I, II, and III mGluRs differentially modulate glutamatergic and dopaminergic signaling.

Double Trouble: Rewired and Unbalanced

Normally, your prefrontal cortex helps with decision-making and impulse control. But repeated drug use weakens this system. The brain keeps getting messages like this drug is great from the reward pathway, while the logical part of your brain can’t shut it down.

So… Can the Brain Ever Go Back?

The scary thing about addiction is how good the brain becomes at remembering drugs. But the hopeful part? The brain is also capable of change. Researchers have found that those same metabotropic glutamate receptors (mGluRs) that help reinforce drug memories might also hold the key to reversing them. By targeting these receptors, it may be possible to rebalance the brain’s glutamate system, reduce cravings, and actually “unlearn” the cycle of addiction.

Here’s what’s exciting:

  • Blocking mGluR5 reduces drug-seeking and relapse in animal studies.

  • Activating mGluR2/3 helps calm excessive glutamate and lowers craving.

  • These strategies work across multiple substances like cocaine, meth, nicotine, and more.

And most importantly, these treatments don’t just patch over symptoms. They work at the cellular level, where addiction takes root. They aim to restore balance in how the brain learns, remembers, and responds to reward.

Addiction Is Brain Health

So yeah, drug use and addiction is scary. It rewires how the brain is rewarded, how the brain learns, and how much impulse control a person has. But the biggest takeaway here is that addiction is not just bad choices—it’s bad brain chemistry.

Understanding the science helps us reframe the narrative. Addiction isn’t a personality flaw. It’s a brain disorder that deserves real treatment and real compassion. The more we know about glutamate, dopamine, and mGluRs, the closer we get to treating addiction like the health condition it truly is.

References:

  1. Mozafari, R., et al. (2023). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder. Progress in Neuropsychopharmacology & Biological Psychiatry.
  2. Siegel, S. (2001). Drug tolerance, cue exposure, and overdose. Addiction Research & Theory, 9(5), 411-419.
  3. Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: A pathology of motivation and choice. Am J Psychiatry, 162(8), 1403-1413.
Uncategorized

Learning How Anxiety is Disrupted Learning

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Artstract created C. Geraci

Do you know someone with an anxiety disorder or do you, yourself, have one? Have you ever wondered what is going awry in the brain to make that happen? To understand this, we need to establish a baseline understanding on how memory formation and consolidation, which is the process of creating a permanent long-term memory, occur.

 

The Anatomy of the Limbic System

The limbic system is the primary part of the brain involved in memory formation and consolidation, and the primary structures within it are the basal ganglia, amygdala, and hippocampus. Each of these structures is portrayed in Figure 1 along with the types of memory they encode, but below each memory type is defined along with its corresponding brain structure.1

  • Basal ganglia:  procedural memory, which remembers how we certain perform tasks.
  • Hippocampus: declarative or explicit memory, which involves remembering things like names, facts, etc.
  • Amygdala: implicit & procedural memory, with implicit memory involving remembrance of things not outrightly spelled out but more likely felt, like emotions.1

 

Figure 1. Illustrates the limbic system’s structures and what types of memory each is involved in creating.1

 

The Hippocampal Formation, Specifically the Dentate Gyrus

Figure 2. Illustrates the anatomy of the dentate gyrus in the hippocampus formation.2

 

The dentate gyrus (DG) is part of something called hippocampal formation, which also encompasses the hippocampus (see Figure 2). It is made of multiple types of cells and is involved in the formation of episodic memory and exploration of new environments.

The three types of cells are dentate granule cells, which are excitatory and use glutamate as their primary neurotransmitter, inhibitory dentate pyramidal basket cells, and excitatory, unmyelinated granule cells called mossy fibers. Mossy fibers synapse onto the CA3 region of the hippocampus, which contains neurons that can then send excitatory signals to the CA1 region of the hippocampus.  However, all these play a role in either exciting or inhibiting hippocampal neuron firing.2

 

The Pathway of Memory Formation, Learning, & Memory Consolidation

Figure 3. Illustrates the different lobes of the cerebral cortex and the cerebellum’s role in memory formation.1

 

Also involved in memory formation are the cerebral cortex and cerebellum, and for information on the cerebellum, click here. The cerebral cortex is where certain memories are stored after the hippocampus has consolidated them, with each lobe corresponding to a different type of memory stored there, as can be seen in Figure 3 above.1

Compiling all the above information, we can create the below pathway that illustrates how memory formation and learning occurs:

  1. Learning begins when sensory signals are transcribed in the cerebral cortex
  2. These signals are transmitted to either the hippocampus, amygdala, and/or dentate gyrus. If to the amygdala or dentate gyrus, they send signals the correlate to how and if the memory is processed by the hippocampus
  3. If the signal is strong or repeated, a long-term memory is consolidated by the hippocampus
  4. The memory is wired back to the cerebral cortex for storage.3

And when you think about it, when you are able to recall how to do something or a fact, that is the outward sign that you’ve accurately consolidated a memory. Aka, you’ve learned something!

 

A Pathway to Anxiety

But in anxiety disorders, such as PTSD or generalized anxiety disorder, some part of this memory formation, learning, and/or consolidation process is disrupted. One study investigated why this is and discovered elevated levels of a dual histone mark called H3S10p-K14ac. This histone mark was found on the promoter regions of the fos and egr1 genes. Essentially, one part of these genes was phosphorylated while another part was acetylated, and what this caused was increased transcription of the fos and egr1 genes, leading to increased anxiety.4

 

Interestingly, the genes with the H3S10p-K14ac dual histone mark were only present in dentate neurons, and when GABAergic inhibitory signals were administered to the DG to block H3S10p-K14ac histone marks from building, symptoms of anxiety decreased. As established earlier, the DG plays a role in telling the hippocampus whether to consolidate a memory or not, so the fact that inhibition of block H3S10p-K14ac histone marks in the DG led to decreased anxiety tells us that something anxiety disorders disrupt the flow of information from the DG to the hippocampus. This makes it so memories cannot be correctly stored in the cerebral cortex, perhaps making them more present in a person’s mind, therefore causing them to feel anxiety in situations where if their memory had been correctly consolidated, they would not be making anxious associations with previously psychologically stressful experiences.4 For more information on how the dual histone H3S10p-K14ac mark forms following psychologically stressful events, click here.

 

Conclusion

Overall, there is a typical pathway by which learning and memory formation occur within the brain, with the limbic system and the cerebral cortex playing a large role in securely storing memories so that we can recall them at appropriate times. But anxiety disorders involve a disruption in this pathway, allowing memories and their associated emotions, like fear, to be at the forefront of someone’s mind at times they wouldn’t normally. Therefore, further research should be done to study what factors are disrupted in each anxiety disorder so that this information can be used to target the root biochemical cause of each disorder.

 

Footnotes:

1https://www.youtube.com/watch?v=yepwx67_UkM

2Shahid, Shahab. “Dentate gyrus.” Kenhub. 2023. https://www.kenhub.com/en/library/anatomy/dentate-gyrus#

3https://www.youtube.com/watch?v=4Hm08ksPtMo

4Reul, M.H.M. Johannes. “Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways.” Frontiers in Psychiatry, vol. 5, no. 5, 2014, doi: 10.3389/fpsyt.2014.00005

Community/Health

Childhood Trauma & Memory

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Traumatic experiences in childhood have a more significant impact on the brain than acute trauma in adulthood. Let’s look into the field of developmental trauma, and one of the ways this is so impactful… memory.

Developmental Trauma

The field of developmental trauma is a new interdisciplinary area of study exploring how traumatic events during childhood affect an individual’s brain and nervous system [1]. 

Developmental trauma is the early, persistent, repeated attacks on healthy development. This includes abuse, neglect, maltreatment, disrupted attachments, exposure to violence, or distress not typical for a child. This type of trauma at such a critical period of development has been found to have a profound impact on the general health and well-being of individuals well into adulthood [2]. The impacts on the mind, brain, and body are not simply outgrown. Childhood trauma causes chronic activation of the stress response system, dysregulating the nervous system, and leading to an imbalanced fight or flight response [1]. This impacts relationships, resilience, and overall worldview. And causes affective, physiological, cognitive, behavioral, self, and relational symptoms [2].

The ACE Study

The first study looking into this correlation was the Adverse Childhood Experiences (ACE) study by the CDC and Kaiser Permanente published in 1998 [3]. This survey asks a series of questions meant to measure how many traumatic events happened in an individual’s childhood. Each question answered ‘yes,’ is one point. Significant evidence supports that increased ACE scores are correlated with decreased overall mental and physical health and well-being. For example, chronic illness, risk-taking behaviors, and suicidality all significantly increase as ACE scores increase. Additionally, individuals with higher ACE scores have a significantly greater chance of dealing with the United States’ top ten leading causes of death [3].

Memory

Artstract created by Hadlie Dahlseid.

One reason trauma is so impactful on anxiety is due to the learning and memory mechanisms of the brain. During a stressful event, glucocorticoid levels are increased, causing stronger associations with the event, and a stronger and longer-lasting memory. Stressors concurrently activate glucocorticoid receptors and NMDA receptors in the dentate gyrus of the hippocampus. When NMDA receptor and glucocorticoid receptor activity converge, histone phosphorylation is impacted. This ultimately leads to gene transcription related to memory consolidation of stressful events [4].

NMDA Receptors

Signaling pathway after activation of glucocorticoid and NMDA receptors [4].
When glutamate binds to a NMDA receptor, an ERK-MAPK signaling pathway is triggered. This is a key pathway involved in learning and memory [4].

Glucocorticoid Receptors

With the release of glucocorticoids, the glucocorticoid receptor interacts with ERK, facilitating the phosphorylation of downstream nuclear kinases, specifically Elk and MSK of the ERK/MAPK pathway. The glucocorticoid receptor acts like a scaffold in this process.

Histones

Next, the glucocorticoid receptor phosphorylates and acetylates histone H3, forming the H3S10p-K14ac mark. These histone modifications are epigenetic mechanisms that lead to altering chromatin structure, promoting the transcription of genes. This results in the entry of immediate-early genes (IEGs) which are essential for memory formation associated with the stressful event [4].  

Dealing with Trauma

So now what do we do with all this information? Trauma-informed care is an approach to social services that recognizes and responds to effects of trauma, while creating a safe space that reduces the risk of re-traumatization [5]. This includes practices to regulate the nervous system, therapies and medications such as those used to treat other anxiety disorders, and understanding the impacts of trauma on the brain and nervous system. Recognizing that trauma is something that happened to someone, not something wrong with someone, is vital. Society needs to shift from asking “what’s wrong with you?” to “what happened to you?”. We can start doing this by understanding the science behind childhood trauma.

References

[1] van der Kolk, B. (2014). The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma. Penguin Books. 

[2] Perry, B. D., & Winfrey, O. (2021). What happened to you?: Conversations on trauma, resilience, and healing. Flatiron Books.

[3] Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., Koss, M. P., & Marks, J. S. (1998). Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults: The Adverse Childhood Experiences (ACE) Study. American Journal of Preventive Medicine, 14(4), 245–258. doi:10.1016/S0749-3797(98)00017-8.

[4] Reul, J. M. (2014). Making memories of stressful events: A journey along epigenetic, gene transcription, and signaling pathways. Frontiers in Psychiatry, 5. https://doi.org/10.3389/fpsyt.2014.00005 

[5] What is trauma-informed care?. University at Buffalo School of Social Work – University at Buffalo. (2024, May 29). 

Uncategorized

EAATs Mechanism Regulating Glutamate Levels In the Brain

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Beyond reviewing the current literature, the paper emphasizes how stress influences memory formation through molecular, epigenetic, and neurobiological mechanisms. It highlights how stress can shape long-term memories and affect future behavior, with implications for psychiatric disorders such as PTSD.

The Excitatory Amino Acid Transporter (EAAT) mechanism plays a crucial role in regulating glutamate levels in the brain, which is essential for maintaining normal brain function and preventing neurotoxicity. Understanding and appreciating the importance of this system is not just a scientific concern—it directly relates to public health, mental well-being, and the potential for developing treatments for neurological and psychiatric disorders.

Why the EAAT Mechanism Matters

1. Glutamate: A Double-Edged Sword

Glutamate is the most abundant excitatory neurotransmitter in the brain. It is essential for learning, memory, and overall communication between neurons. However, too much glutamate in the extracellular space becomes toxic—a condition called excitotoxicity, which damages or kills neurons.EAATs prevent this by rapidly clearing excess glutamate from synapses after neurotransmission, maintaining safe concentrations and protecting neurons1.

Figure 1. Glutamate-glutamine cycle. Glutamate (Glu−) released after excitatory transmission is collected by astrocytic EAAT transporters 1 and 2. The glutamate is then either converted into α-ketoglutarate (α-KG) via glutamate dehydrogenase (GDH) or transaminase reaction and enters the TCA cycle, or else is converted into glutamine (Gln) by glutamine synthetase (GS). Astrocytes excrete Gln back into the extracellular environment via the Na+ driven SNAT3 transporter, which is then taken up by an as yet unconfirmed neuronal Gln transporter. Neurons then convert Gln back to Glu− via a phosphate-activated glutaminase (PAG) reaction to replenish their vesicular Glu− stores.

Public Health Implications

When EAAT function is impaired, it can contribute to a range of devastating neurological and psychiatric disorders, such as:

  • Alzheimer’s disease

  • Amyotrophic lateral sclerosis (ALS)

  • Epilepsy

  • Schizophrenia

  • Stroke-related brain injury

Understanding EAATs helps in designing drugs or therapies that could regulate glutamate levels more effectively and prevent or treat these conditions2.

Mental Health and EAATs

Studies have also linked EAAT dysregulation to mood disorders like depression and anxiety. In fact, some antidepressants may act (in part) by modulating glutamate levels or transporter function3. A healthy glutamate balance ensures stable mood, cognition, and neural resilience.

Future Therapies and Personalized Medicine

The public should care because EAATs are potential therapeutic targets. Research in this field is paving the way for precision medicine that could help people based on their specific transporter function, especially those with genetic mutations affecting EAAT expression4.

Why This Topic Deserves Public Attention

  • Neurodegeneration affects millions and leads to costly healthcare burdens.

  • Mental health disorders are rising, and glutamate imbalance plays a role in many of them.

  • Increased public understanding can lead to support for neuroscience research and better health policy.

  • Families affected by diseases like ALS, Alzheimer’s, or epilepsy stand to benefit from breakthroughs in EAAT-targeted treatments.

Footnotes

  1. Danbolt, N. C. (2001). Glutamate uptake. Progress in Neurobiology, 65(1), 1-105. https://doi.org/10.1016/S0301-0082(00)00067-8

  2. Rothstein, J. D., Dykes-Hoberg, M., Pardo, C. A., et al. (1996). Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron, 16(3), 675–686. https://doi.org/10.1016/S0896-6273(00)80086-0

  3. Sanacora, G., Zarate, C. A., Krystal, J. H., & Manji, H. K. (2008). Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews Drug Discovery, 7(5), 426–437. https://doi.org/10.1038/nrd2462

  4. Choudary, P. V., Molnar, M., Evans, S. J., et al. (2005). Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. PNAS, 102(43), 15653–15658. https://doi.org/10.1073/pnas.0507901102

Uncategorized

Dopamine and Glutamate: The Dynamic Duo Behind Your Brain’s Biggest Hits

Posted on by Nessa Angau / 0 Comment
An abstract by Venesa Angau

 

Imagine you’re at a concert. The air is buzzing, the bass is thumping, and the crowd is alive. The excitement of anticipation builds as the lights dim and the first chords strike. Every beat pulses through your body, connecting you to the thousands around you. In your brain, a similar concert is happening every time you feel joy, excitement, or even the rush of a risky decision. The headliners? Dopamine and Glutamate — the dynamic duo behind your brain’s greatest hits.

The Beat

Dopamine is like the lead singer of the band, basking in the spotlight. It’s the neurotransmitter responsible for that euphoric feeling when you accomplish something or indulge in a pleasurable experience. Whether it’s a bite of chocolate cake or a victory dance after scoring a goal, dopamine is right there, dropping the beat.

But no concert is complete without the hype-man hyping. Enter Glutamate — the brain’s primary excitatory neurotransmitter. While dopamine signals pleasure, glutamate amplifies the experience, strengthening connections between neurons. It’s the reason you remember the way that cake tasted or the thrill of that winning moment. Glutamate makes sure those memories stick, playing a key role in learning and reinforcement.

The interplay between dopamine and glutamate is most evident in the brain’s reward circuitry. At the heart of this circuit is the nucleus accumbens, often referred to as the brain’s “pleasure center.” When you engage in a rewarding activity, dopamine floods this region, signaling a positive experience. Meanwhile, glutamate, originating from areas like the prefrontal cortex and amygdala, reinforces the memory of the experience and the associated cues. This coordination ensures that behaviors linked to pleasure are remembered and likely repeated. However, addictive substances can hijack this process, leading to overstimulation of the nucleus accumbens and creating strong, maladaptive memories that drive compulsive drug-seeking behaviors [1].

The Catch: When the Beat Gets Twisted

An abstract by Venesa Angau

But here’s the twist. Just like an over-amped concert can get chaotic, an imbalance between dopamine and glutamate can throw the brain into disarray. This is exactly what happens with addictive substances like nicotine, cocaine, or methamphetamine. These drugs hijack the soundboard, cranking up dopamine to extreme levels while distorting glutamate’s role.

Instead of a balanced duet, dopamine takes over, blaring constant reward signals. Glutamate, meanwhile, reinforces those memories, creating strong neural pathways that scream, “More, more, more!” This combination rewires the brain, making cravings feel impossible to resist.

The longer this cycle continues, the more difficult it becomes to restore balance. Over time, the brain’s natural dopamine production may dwindle, leaving individuals feeling joyless without the substance. Meanwhile, the heightened glutamate signaling remains like a haunting encore, pushing the desire to use again. This explains why even after quitting, people often experience intense cravings and a heightened sensitivity to triggers.

Additionally, the prefrontal cortex, responsible for decision-making and self-control, weakens under the constant strain. It’s like the sound engineer abandoning their post, leaving the music to spiral out of control. Without the brain’s natural ability to regulate impulses, resisting cravings becomes a monumental challenge.

A New Track: Restoring the Harmony

News&Views
Figure 1. Diagram showing the interaction of dopamine & glutamate

 

Therefore, researchers are tuning into ways to restore this balance. Metabotropic glutamate receptors (mGluRs), especially those in Group II, act like sound engineers, turning down the volume of excessive glutamate release. By targeting these receptors with medications, scientists hope to weaken the overpowering neural pathways that drive addiction [2].

Drugs like LY379268 are showing promise in preclinical trials. They calm the overstimulated circuits, reducing cravings and preventing relapse. Think of it as a gentle fade-out of that relentless craving track, making space for healthier rhythms to emerge [3].

The Final Encore

So next time you savor a delicious meal or celebrate a win, remember dopamine and glutamate are behind the scenes, delivering a symphony of experience. And just like a perfectly balanced concert, when these neurotransmitters play in harmony, the brain’s greatest hits keep on coming.

But when the balance goes awry, science is working on remixing the track. Because everyone deserves a standing ovation  for the brain, and all the brilliance it contains.

Resources

[1] Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016). The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis. Pharmacological Reviews, 68(3), 816–871. https://doi.org/10.1124/pr.116.012484

[2] Taepavarapruk, P., Butts, K. A., & Phillips, A. G. (2014). Dopamine and Glutamate Interaction Mediates Reinstatement of Drug-Seeking Behavior by Stimulation of the Ventral Subiculum. International Journal of Neuropsychopharmacology, 18(1), pyu008–pyu008. https://doi.org/10.1093/ijnp/pyu008

[3] Cannella, N., Halbout, B., Uhrig, S., Evrard, L., Corsi, M., Corti, C., Deroche-Gamonet, V., Hansson, A. C., & Spanagel, R. (2013). The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior. Neuropsychopharmacology, 38(10), 2048–2056. https://doi.org/10.1038/npp.2013.106

Community/Disease/Health

Psychostimulant Addiction: A Learning Disease

Posted on by Meg / 0 Comment

You may have heard that addiction is a disease, but this disease uniquely harms the body – it attacks learning. 

Psychostimulant Use Disorder (PUD) is a chronic, relapsing condition characterized by compulsive drug-seeking behavior despite negative consequences[1]. Despite its prevalence, there are no FDA-approved medications specifically for treating PUD. Recent research, however, has pinpointed metabotropic glutamate receptors (mGluRs) as key players in the neuroplastic changes underlying addiction. “A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder”[2] delves into how these receptors modulate synaptic plasticity in brain reward circuits following psychostimulant use. This blog post will break down the science highlighted in the article and discuss possible therapeutic interventions for PUD. 

Addiction hijacks the brain’s reward system, which includes the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and amygdala. Psychostimulants like cocaine, amphetamines, and nicotine disrupt glutamate signaling (the brain’s primary excitatory neurotransmitter) leading to long-term synaptic changes[2]. These synaptic changes are extremely similar to those observed in learning. Instead of learning a new word in Spanish, a mathematics formula, or a fun psychology fact, the brain is learning that psychostimulant use feels good. These positive feelings are due to the drugs increasing extracellular dopamine and glutamate, reinforcing drug-associated memories and cravings. Glutamate acts through two receptor families: ionotropic receptors (fast-acting ligand-gated channels) critical for synaptic plasticity, and metabotropic receptors (mGluRs, which are G-protein coupled receptors) that modulate synaptic strength over longer time periods. The review focuses on mGluRs, divided into three groups based on signaling pathways and localization.

Group I mGluRs (mGluR1/5): Synaptic Potentiation and Relapse

Group I mGluRs are located postsynaptically and are linked to Gq proteins. They activate phospholipase C (PLC) and PKC, which hydrolyze PIP2 into DAG and IP3. These intracellular events create various outcomes depending on the psychostimulant.

  • Role in PUD:
    • Cocaine: Enhances long-term potentiation in the NAc and PFC. Antagonists reduce drug-seeking, while agonists promote relapse.
    • Amphetamines: Increase mGluR5 expression in the PFC, correlating with conditioned place preference.
    • Nicotine: mGluR5 blockade via antagonists attenuates nicotine self-administration and reward[2].

Group II and III mGluRs (mGluR2/3/4/6/7/8): Presynaptic Inhibition

Group II and III mGluRs are located presynaptically. They are Gi/o-coupled, which function to inhibit glutamate release (dampening the effects of the drugs) by decreasing cAMP and adenylyl cyclase levels. As with Group I, the intracellular inhibition creates varying effects depending on the type of drug.

  • Role in PUD:
    • Cocaine: Agonists inhibit relapse by normalizing hyper-glutamatergic states in the NAc. mGluR7 activation inhibits relapse by reducing glutamate release in the NAc.
    • Methamphetamine: Downregulation of mGluR2/3 contributes to cravings, and agonists reduce reinstatement. mGluR8 expression changes may counteract drug-induced plasticity.
    • Nicotine: Activation in the VTA decreases nicotine-seeking behavior[2].

Figure 1. An illustration of mGluR localization in reward circuitry and synapses [2].
Repeated drug use alters dendritic spine density and synaptic strength in reward circuits. For example, cocaine increases AMPA/NMDA ratios in VTA dopamine neurons, a hallmark of long-term potentiation (LTP; aka learning). Additionally, nicotine enhances hippocampal LTP via mGluR5[2]. These changes underlie the persistence of drug memories, making relapse a formidable challenge. Such changes are why addiction is a disease of learning. 

Just as we are able to learn, we are able to unlearn. Viewing addiction as a problem with learning, association, and rewards provides possible promising therapeutic implications for something that is currently untreatable by medication. Targeting mGluRs offers a nuanced approach, and the article notes that Group I antagonists may prevent cue-induced cravings, Group II agonists could restore glutamate homeostasis, and Group III modulation might disrupt drug-associated memories[2]. Taken together, targeting mGluRs may have promising therapeutic benefits. 

Figure 2. An illustration of long-term potentiation at the synapses. Synaptic plasticity can cause an increase in the amount of neurotransmitters released or the number of post-synaptic receptors available [3].

The review highlights mGluRs as critical mediators of addiction-related neuroplasticity. While recent research is promising, translating these findings into treatments requires further research, especially given the complexity of glutamate signaling across brain regions and its importance in a variety of normal brain functions. For now, mGluRs remain a hopeful future direction in curing PUD. 

Addiction rewires the brain and creates a learned dependence on and craving for drugs, but by hacking glutamate’s mGluRs, researchers may just reset the system. Therefore, researching the therapeutic effects of mGluR agonists and antagonists is essential for combating PUD. 

 

References

 

[1] “Stimulant Use Disorder > Fact Sheets > Yale Medicine.” Accessed: Apr. 02, 2025. [Online]. Available: https://www.yalemedicine.org/conditions/stimulant-use-disorder

[2] R. Mozafari, S. Karimi-Haghighi, M. Fattahi, P. Kalivas, and A. Haghparast, “A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder,” Prog. Neuropsychopharmacol. Biol. Psychiatry, vol. 124, p. 110735, Jun. 2023, doi: 10.1016/j.pnpbp.2023.110735.

[3] “Long-term synaptic plasticity.” Accessed: Apr. 02, 2025. [Online]. Available: https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/long-term-synaptic-plasticity

 

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Addicted

Posted on by rhurley1 / 0 Comment

The article we have covered in a previous week, “A role on the metabotropic glutamate receptors in neuroplasticity” by Roghayeh Mozafari, Saeidah Karimi-Haghighi, Mojdeh Fattahi, Peter Kalivas, and Abbas Haghparast was an article about the basics on psychostimulant use disorder as an addiction disorder. Basically, it is a growing public problem attached with both physical and mental handicaps. However, the article warns that there is currently very little we can really do for psychostimulant use disorder, so it is essential to obtain all micro-scale information we can gather on all related topics from reward to many others.The topic today is why people should care about this topic and what the people must know, so without further ado let’s get reading!

The article informs us of some of the distinguishable characteristics of psychostimulant use disorder connected to the micro-scale levels of small. Though, the article specifically focuses mainly on neuron circuitry and glutamate receptors.^1 As a result of this connection, we can now classify correlation here.

Figure one from the article mentioned above is especially excellent at explaining this where it was needed (excellently timed, or in other words placed well). That piece is simultaneously even an absolutely massive diagram which shows even a seemingly full diagram of the journey of glutamate in the brain going off of glutamate receptors activation. Although, one slight problem could be that it could feel a large bunch overwhelming if you’re not too familiar with the applied terms of figure two in the Neuroscience field. This was an excellent piece to me for it is maximized simplicity because, for clear reasons, that kind of thing strongly helps. The figure may also benefit people uninvolved in Neuroscience as well because figure one works similarly like speech bubbles in comic books with all the brief, yet descriptive, labeling, and I find that effective myself in general because it’s easy on the eyes to track or logicate.

Now, at this point, one, such as yourself, may wonder why people really should care about all the above information. Well, let’s answer with essential basics to answer ourselves by quickly asking ourselves something simpler first; what really is a stimulant disorder? Well, the answer is absolutely nothing short of a true tragedy. According to the U.S. Department of Veterans Affairs, stimulant use is known as the situation where a person is addicted to a drug for an innate reward (think cocaine, methamphetamine, amd even ritalin) with a consequence of serious health risks with the worst listed being, “heart attack, stroke,…”^2 that in turn becomes medical emergencies. Considering that we know about these symptoms as a consequence, it’s no shock to pretty much anyone that such a scenario can turn serious fast. Let us put this into perspective with another topic.

In my class, I personally examined the neurodiverse populations adapting to addictions. Unsurprisingly, I learned from Help 4 Addiction that neurodiverse populations get whole new different symptom addictions compared to the common neurotypical (such as lower functioning symptoms, long term executive functioning struggles, and so on)^3. However, it gets far worse than that; you may recall what I call “reinforcement culture” where people often magnetize towards others with similar addictions (think coffee, sugar, and especially alcohol) which makes it harder to make friends if you do not share an addiction (nor at least part takes). Well, neurodiverse populations such as autistic populations have an increased risk to addictions compared to neurotypicals.

References:
1.) “A role on the metabotropic glutamate receptors in neuroplasticity” by Roghayeh Mozafari, Saeidah Karimi-Haghighi, Mojdeh Fattahi, Peter Kalivas, and Abbas Haghparast
2.) https://www.mentalhealth.va.gov/substance-use/stimulants.asp
3.) https://www.help4addiction.co.uk/addiction-and-neurodiversity/

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Hijacked Happiness: How Addiction Rewires the Brains Reward System

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HIJACKED HAPPINESS: HOW ADDICTION REWIRES THE BRAINS REWARD SYSTEM 

Addiction hijacks the brain’s reward circuits, reshaping the very wiring that governs pleasure and motivation. Key areas such as the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and amygdala—which are normally involved in reinforcing survival behaviors like eating or socializing—are overtaken by psychostimulants. These drugs flood the brain with dopamine, causing compulsive drug-seeking behaviors and diminishing the sensitivity to natural rewards. Glutamate, another neurotransmitter crucial for synaptic plasticity, is disrupted, leading to long-lasting changes that reinforce addiction and heighten vulnerability to relapse. By targeting neurotransmitter systems, innovative treatments can help restore balance in the reward circuitry, offering hope for those suffering from psychostimulant use disorder. [1]

WHAT IS PUD?

Psychostimulant Use Disorder (PUD) is a chronic, relapsing condition characterized by an uncontrollable drive to consume psychostimulants, even in the face of negative emotional and physical consequences. It causes profound neuroadaptations within the glutamatergic circuitry responsible for reinforcement and reward processing, resulting in physical and mental impairments. Psychostimulants include a range of substances such as nicotine, cocaine, methamphetamine, MDMA, dextroamphetamine, and methylphenidate—all of which trigger extensive changes in glutamate transmission and receptor function, playing a pivotal role in both the development and persistence of PUD.

Fig.1 image of pills

 

THE ROLE OF THE REWARD CIRCUIT

 The brain’s reward system comprises interconnected regions—the VTA, NAc, PFC, hippocampus (HPC), and amygdala (AMY)—that work together to encourage survival behaviors like eating and socializing to give us feelings of pleasure and motivation. However, psychostimulants exploit these circuits, driving the transition from initial drug use to addiction. Dopaminergic neurons in the VTA regulate glutamate and GABA neurotransmission, ensuring balance in the brain’s signaling. When this balance is disrupted, addictive behaviors become deeply ingrained.[2] The interactions among various parts of this circuit and neuroadaptations in these areas mainly contribute in the rewarding impact of drugs and to the progression from initial drug use to PUD’s.

Fig.2 cocaines response in the brain, involving glutamate and GABAminergic neurons.

 

GLUTAMATE: THE MAIN NEUROTRANSMITTER

Glutamate is the brain’s most abundant excitatory neurotransmitter, making up about 70–90% of the brain’s synaptic communication.  Glutamate helps neurons “talk” to each other quickly, which is essential for processes like learning, memory, and overall brain function.

Its role in addiction is profound, as glutamate projections from the prefrontal cortex (mPFC) and amygdala to the NAc directly influence GABAergic activity, which regulates dopamine transmission. Different glutamate receptors—including NMDA, AMPA, kainate, and metabotropic receptors (mGluRs)—are involved in addiction-related neuroadaptations, highlighting the complexity of glutamatergic involvement in psychostimulant use disorder. This ability to rapidly transmit signals also plays a key role in synaptic plasticity, the brain’s way of adapting and changing based on experiences.

Metabotropic glutamate receptors (mGluRs)—classified I, II, and III—play a key role in synaptic plasticity within brain reward circuitry. These G-protein coupled receptors are distributed throughout the peripheral nervous system and interact with psychostimulants such as cocaine, amphetamines, methamphetamine, and nicotine.

Beyond addiction, glutamate is vital for learning and memory. Changes in glutamate function not only influence recall and cognitive adaptability but also contribute to the development of addictive behaviors. Among the crucial receptors involved in synaptic plasticity and addiction are:

  • NMDA and AMPA receptors: Facilitate fast excitatory signals.
  • Kainate and metabotropic glutamate receptors (mGluRs): Engage in more intricate signaling processes.

SYNAPTIC PLASTICTY– ADDICTION

Addiction is more than physical dependency—it’s deeply intertwined with memory and learning processes, particularly in the hippocampus (HPC), the brain’s center for memory. A key concept that explains addiction’s impact on the brain is synaptic plasticity, which refers to the brain’s ability to strengthen or weaken connections between neurons over time. This dynamic process shapes how we learn, remember, and even how addiction memories persist—playing a critical role in relapse.

Types of Synaptic Plasticity:

  1. Structural Plasticity: This involves physical changes in the brain, like the formation or pruning of dendrites and synapses, which are the  connections between neurons.
  2. Functional Plasticity: The brain’s ability to shift functions from damaged areas to healthier regions, allowing it to adapt to new situations.

In the case of addiction, the brain’s natural adaptability is exploited, creating powerful neural circuits that are tied to drug-seeking behaviors. Over time, addiction essentially “rewires” the brain’s reward and memory systems to prioritize substance use.[3]

HOW SYNAPTIC PLASTICITY DRIVES ADDICTION 

  • Repeated drug use reinforces synapses linked to drug-related cues, such as specific sights, smells, or environments. This process, largely driven by Long-Term Potentiation (LTP), occurs in key brain regions like the hippocampus (HPC), nucleus accumbens (NAc), and ventral tegmental area (VTA). Over time, these circuits become deeply ingrained, fueling compulsive drug-seeking behaviors.
  • Drugs overwhelm the brain with dopamine, dulling its responsiveness to everyday pleasures like eating or socializing. Long-Term Depression (LTD) affects neural circuits linked to natural rewards, effectively rewiring the brain to prioritize substance use over other activities.
Fig 3. Limbic reward pathway shown on brain

 

WHAT IS LTP?  LONG TERM POTENTIATION 

LTP is the process by which synaptic connections are strengthened after repeated stimulation. It’s crucial for learning and forming long-lasting memories.  LTP helps solidify the connection between drug-related cues (like people, places, or paraphernalia) and the pleasurable high that comes with using substances. This means that even after a period of abstinence, these “reinforced” memories can quickly resurface when exposed to these triggers, increasing the risk of relapse.

WHAT IS LTD? LONG TERM DEPRESSION

LTP is the  weakening of synaptic connections after low-frequency stimulation. It allows the brain to “forget” less relevant information over time. Addiction shows that  LTD can suppress memories tied to natural rewards, like the joy of spending time with loved ones. Over time, this creates an imbalance where drug-related rewards take precedence, further cementing the addictive behavior and making it harder to return to normal, healthy reward patterns. [4] 

NEUROPLASTICITY FOR RECOVERY 

The psychostimulant-induced behavioral and neurological plasticity could potentially explore circuit and molecular targets with the potential to contribute to the treatment of PUD. To date, there are no FDA-confirmed medicines for the treatment of psychostimulant abuse; therefore, clarification of the cellular and molecular alterations participating in PUD is crucial for developing beneficial medications.

Short- and long-term adaptive changes in dopamine transmission and brain circuitry have been extensively studied as mediators of PUD and its associated neuropsychiatric impairments. These studies underline the importance of neurotransmitter synthesis and release in various parts of the reward circuit, which are significantly altered by prolonged drug use. Such disruptions are primary contributors to the cognitive and behavioral impairments seen in individuals with PUD.

Innovative treatments targeting glutamate receptors or excitatory amino acid transporters (EAATs) offer promising pathways to normalize synaptic transmission and reduce cravings. By restoring balance within the reward circuitry and addressing neuroplastic changes, these therapeutic approaches could play a critical role in reshaping the future of addiction recovery.

Fig 4. Drawing of man and pills

REFERENCES

Cooper, S., Robison, A. J., & Mazei-Robison, M. S. (2017). Reward Circuitry in Addiction. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 14(3), 687–697. https://doi.org/10.1007/s13311-017-0525-z

Kalivas, P. W., Lalumiere, R. T., Knackstedt, L., & Shen, H. (2009). Glutamate transmission in addiction. Neuropharmacology, 56 Suppl 1(Suppl 1), 169–173. https://doi.org/10.1016/j.neuropharm.2008.07.011

Mozafari, R. et al, (2023) A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder, Progress in Neuro-Psychopharmacology and Biological Psychiatry,Volume 124. https://doi.org/10.1016/j.pnpbp.2023.110735

Puderbaugh, M. (2023, May 1). Neuroplasticity. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK557811/

 

FOOTNOTES

[1] Kalivas, P. W., Lalumiere, R. T., Knackstedt, L., & Shen, H. (2009). Glutamate transmission in addiction. Neuropharmacology, 56 Suppl 1(Suppl 1), 169–173. https://doi.org/10.1016/j.neuropharm.2008.07.011

[2] Cooper, S., Robison, A. J., & Mazei-Robison, M. S. (2017). Reward Circuitry in Addiction. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 14(3), 687–697. https://doi.org/10.1007/s13311-017-0525-z

[3] Puderbaugh, M. (2023, May 1). Neuroplasticity. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK557811/

[4]  Mozafari, R. et al, (2023) A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder,Progress in Neuro-Psychopharmacology and Biological Psychiatry,Volume 124.https://doi.org/10.1016/j.pnpbp.2023.110735

 

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Hijacked by Reward: How Addiction Rewires the Brain and What We Can Do About It

Posted on by adebleye / 0 Comment

Picture this: you’re at a party, feeling great, laughing with friends. Someone hands you a drink—or something stronger—and says, “Just try it. You’ll feel amazing.” You do. And in that moment, your brain lights up like a Christmas tree. You don’t realize it, but your brain is quietly rewiring itself. Not for pleasure—though that’s how it starts—but for need. For survival. That’s how addiction begins.

This week in Cobbers on the Brain, we explore the compelling science behind this transformation in our brains, through Nora Volkow’s groundbreaking review on the neuroscience of drug reward and addiction. Addiction isn’t simply about poor decisions or “bad habits.” It’s about a fundamental hijacking of our brain’s reward system. And once that system is altered, the line between want and need blurs into something far more dangerous.

Let’s start with the basics. Our brains are built to seek out things that ensure our survival—food, water, connection. These activities trigger the release of dopamine, a feel-good neurotransmitter that acts like a chemical “thumbs up,” reinforcing behavior so we repeat it. This loop is vital: dopamine helps us learn what’s worth doing again.

But drugs like cocaine, opioids, nicotine, and alcohol flood the brain with dopamine in ways that natural rewards simply can’t match. The ventral tegmental area (VTA) and nucleus accumbens (NAc)—two key regions of the brain’s mesolimbic reward pathway—light up like fireworks when drugs are introduced. Over time, this hyperstimulation starts to reshape the brain’s wiring, creating strong associations between the drug, the environment, and the experience of reward.

Here’s the paradox: the more someone uses a drug, the less pleasure they feel from it. Over time, dopamine levels don’t rise as dramatically with drug use—but the cues that remind someone of the drug (a lighter, a party, a memory) still do. These cues trigger craving, not satisfaction. And that craving becomes unbearable. It’s not about getting high anymore—it’s about not feeling miserable.

Addiction shifts from pleasure-seeking to survival-seeking, not because people are weak, but because their brains are operating on a new set of rules. The prefrontal cortex, the area responsible for judgment, impulse control, and decision-making, loses its regulatory grip. And so, even when someone desperately wants to quit, their brain is shouting louder: “You need this. Now.”

This explains why addiction is a chronic relapsing disease—not a moral failing. It’s a neurobiological condition that demands compassion, science-based treatment, and long-term care strategies.

This brings us to the second article, a fascinating review on metabotropic glutamate receptors (mGluRs)and their role in neuroplasticity following psychostimulant use disorder (PUD). These receptors help modulate glutamate, the brain’s main excitatory neurotransmitter, and play a crucial role in learning, memory, and motivation.

While dopamine gets most of the attention, glutamate is the hidden architect of addiction—laying down the long-term wiring changes that make addiction so persistent. mGluRs act like dimmer switches for glutamate transmission and are found throughout the brain’s reward system, including the prefrontal cortex, amygdala, and hippocampus.

Research shows that activating or inhibiting specific mGluRs can reduce drug-seeking behavior, block relapse triggers, and even enhance the brain’s ability to unlearn the powerful conditioning that ties drugs to environmental cues. Drugs that modulate these receptors—called positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs)—are being explored as promising treatment options for cocaine, methamphetamine, and nicotine addictions.

Addiction isn’t something that happens to “other people.” It’s affecting our neighbors, our classmates, our families. The opioid epidemic alone has claimed hundreds of thousands of lives in the U.S. alone. And yet, shame and stigma often silence those struggling, even as their brains scream for help.

Understanding the neuroscience of addiction humanizes the condition. It tells us that this isn’t about “just saying no.” It’s about unlocking the mechanisms of craving, relapse, and recovery—and using that knowledge to create treatments that actually work.

So what should you take away from all this?

Addiction is preventable. It’s treatable. And it’s not about being strong or weak—it’s about the brain’s incredible, but vulnerable, capacity to adapt. With continued research into dopamine, glutamate, and beyond, we can shift the narrative—from blame to biology, from punishment to progress.And maybe, just maybe, we can build a world where people have a better chance of getting their lives back.

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