Cobbers on the Brain

Anxiety can be characterized by many different symptoms an individual my experience. From nervousness when talking in front of a large crowed to test taking, these stressful situations can significantly increase and interfere with daily activities. When this occurs, individuals may experience excessive worry, emotional distress, and severe anxiety. Such symptoms are diagnosed as generalized anxiety disorder. In the United States, 40 million adults experience some form of anxiety disorder, most starting before they even turn 21 years old. 

Figure 1.

This number doesn’t specifically refer to the generalized anxiety disorder prevalence, but it does provide an overview of the commonality of anxiety disorders. That being said, there are many types of anxiety that individuals may experience, from generalized anxiety disorder, panic disorder, social anxiety, and specific phobia. Theses are the top leading types of anxiety experienced by people today.

In order to come up with these diagnoses scientists must perform studies an animal models in order to find a baseline for symptoms of anxiety. One way researchers can do this is by conducting a Morris water maze test. Morris water maze test is a conduct strategy generally utilized with rodents. It is generally utilized to conduct spatial learning and memory. It empowers learning, memory, and spatial attempting to concentrate with extraordinary exactness, and can likewise be utilized to survey harm to specific cortical areas of the cerebrum. It is utilized by neuroscientists to quantify the impact of neurocognitive problems on spatial learning and conceivable neural medicines, to test the impact of sores to the mind in territories worried about memory, and to concentrate on how age impacts intellectual capacity and spatial learning. The errand is additionally utilized as an apparatus to consider drug misuse, neural frameworks, synapses, and mental health. 

Figure 2.

There are three phrases used to test the Morris water maze: 

Training phase-    

Escape latency is how much time it takes to find the platform  

Wall hugging can measure the rat not learning or anxiety  

Swim speed can measure how drugs change swim speed and how long it takes to find the platform  

Swim pattern shows the search strategy  

Probe trial-   

Time in target-the removal of the platform can see if the rat is using a strategy to find the general area of the platform when it doesn’t know where it is vs. the rat knowing where it is using a special strategy  

Quadrant-   

Tracks how much time the rat spends on the platform 

The Morris water maze test is one of the most regularly utilized conduct tests to quantify spatial learning in rodents, including rodents and ordinary and hereditarily adjusted mice. It was first evolved and revealed by Richard G. Morris to test the spatial learning conduct of rats. He demonstrated that a hippocampal injury would weaken spatial learning. The test device comprises of a roundabout water tank filled with hazy water and a shrouded stage submerged a couple of centimeters under the water surface in one quadrant of the tank. The tank is encircled by viewable signals. Preparing the creatures to find the concealed stage may take a couple of days (normally 5–7 days). In each preparation preliminary, the test creature is permitted to swim in the water for 5 minutes to locate the shrouded stage. On the off chance that the creature doesn’t discover the stage within the 5-minute time frame, it is safeguarded and set on the stage. Every creature at that point goes through 5 minutes on the stage before being gotten back to its home cage. Every creature has five instructional courses a day. Given that the stage is covered up, the creature must figure out how to utilize the viewable signals encompassing the pool to find the stage. As preparation advances, the time used to locate the shrouded stage will ordinarily diminish. Such diminished break latencies will most regularly mirror the reception of a central inquiry methodology for creatures with no disability in spatial learning. Notwithstanding decreased getaway latencies may likewise mirror the selection of non-spatial methodologies (e.g., mice may figure out how to swim in concentric circles a fixed good way from the divider). In this manner, to separate spatial and non-spatial systems, mice are normally given a test, where the stage is eliminated from the pool, and the mouse is permitted to look for it, commonly over a 60-second time span. Mice having received a spatial procedure will center their pursuit close to the previous area of the stage.

Figure 1: The chemical structure of propranolol.

The use of propranolol

The most commonly prescribed medications typically tend to be those that target immediate health issues such as pain or heart problems. Propranolol is one such medication that is common prescribed for hypertension, coronary artery disease and tachyarrhythmias. However, this medication can readily enter through the blood brain barrier, so there uses can be much more then simply an heart medication.

Figure 2: Diagram of the blood brain barrier.

Mechanism of action

As seen in Figure 2 above, the blood brain barrier can be pretty tricky to cross. So, those medications that can offer a cascade of treatment possibilities. In the case of propranolol, it is a β 1,2-adrenoreceptor antagonist which will compete at the receptor level with catecholamines, thus blocking their effect. This mechanism has also been deployed to block β1,2-adrenoreceptors in the central nervous system. So, it is through the blocking of the catecholamines (adrenaline, noradrenaline, and dopamine) from binding to their corresponding adrenoreceptors that propranolol is able to reduce anxiety.

Figure 3: Commonly used SSRIs used in treatment of anxiety and depression

Why isn’t propranolol prescribed for anxiety?

While the use of propranolol offers many promising results in both animal models and its use in humans, the world of treatment went a different route in the treatment of anxiety. The more recent prevalence of selective serotonin reuptake inhibitors (SSRIs) took the scene before propranolol could be effectively implemented for the treatment of anxiety. SSRIs, as the name implies, act to block the reuptake of serotonin in the synaptic cleft after it has been released. The presence of serotonin in the synaptic cleft has been proven to be an effective treatment for an assortment of disorders, but I’m mainly focusing on anxiety. So, it isn’t so much that propranolol isn’t used because it isn’t effective, but rather because there are more popular substitutes instead.

Figure 4: Generalized pathway for how stimuli is converted into long-term memories.

Function relating to memory

For the article we discussed in class, we mostly looked at how anxiety and stressful situations contribute to memory. This was seen with the use of the forced swim test as the stressful situation led to an increase in memory of the test as well as a corresponding change in behavior (reduced time to begin the immobile phase of the forced swim test). To continue with the idea of anxiety and memory, propranolol actually has an effect on this too!

As seen in Figure 4 above, there is a consolidation step that occurs after short-term memory that helps to convert sensory stimuli into long-term storage. This typically involves protein synthesis. Propranolol acts by selectively inhibiting this protein synthesis of fear inducing stimuli so that the fear memory is unable to be reconsolidated and converted into a long-term memory. It is believed that the selectivity acts by inhibing the feeling of fear in the memory, but leaving the overall memory of the stimulus otherwise unchanged.

The use of propranolol

As discussed above, propranolol is a commonly prescribed heart medication that also has to ability to help treat anxiety disorders, quite effectively. However, because of SSRIs shared ability to cross the blood brain barrier and the increased popularity of SSRIs, propranolol has been reduced to being prescribed for heart problems. But who knows, maybe in those that do have it prescribed, it is doing wonders!

For more information about propranolol, please see the following article here.

Also included is an artstract. I have a couple friends with diagnosed anxiety disorders and when I asked them what it felt like, they said they just get so overwhelmed by nothing and everything at the same time. So , I tried to get that in my drawing.

Whether we like it or not, the film industry has always had a significant influence on the representation, as well as our understanding of mental illness. With the popularity of Hollywood comes both, positive and many negative consequences.

Movies, such as Split are said to have done more harm than good in trying to show and destigmatize personality disorders. Split, while tackling dissociative identity disorder (DID), has been officially categorized under “schizophrenia movies” by Google. Another example that is categorized under the same genre and adding to the confusion is the movie Shutter Island, in which some might argue it is DID that is being represented, or even Delusional Disorder rather than Schizophrenia. It seems as though movies that show DID are commonly mistaken for showing schizophrenia. As one might imagine, mislabeling and miscathegorizing movies is quite problematic for various reasons, the most important one being that they are two completely different mental disorders. How? – you might say, so let’s look at them now.

What may be the cause of schizophrenia?

As indicated in the table, one of the major differences is that DID is mostly associated with traumatic life experiences, while schizophrenia is mainly associated with genetic factors. Given the significant focus of research on the biological background of this disorder, we are able to suggest some explanations as well as offer pharmacological treatment.

The above visual is showing a cell signaling pathway, the Wnt/B-catenin pathway, which plays an important role in early development. Dopamine is a key regulator of this signaling cascade, and in the event of increased levels it can lead to abnormally high levels of GSK3 and B-catenin, resulting in the overall inhibition of the pathway. This inhibition results in low levels of TCF/LEF, which are transcription factors at the end point of the Wnt signaling cascade, and are involved in growth. Schizophrenic patients presented with higher than normal levels of dopamine, and researchers thus have concluded that the disruption of this signaling pathway may result in the development of schizophrenia.

So, what now?

While there is no cure for schizophrenia at this time, doctors are able to offer various treatment options.

1. Psychosocial Interventions

• • Therapy
    • Individual and/or family therapy are amongst the options, as well as something called an electroconvulsive therapy.
  • Skills training
    • Behavioral skills training (BST) is a method frequently used by many applied behavior analysts in order to teach skills one might be lacking due to mental illness(es).

2. Pharmacological treatment

• • Antipsychotics
    • First and second-generation antipsychotics are targeting dopamine in the signaling pathway.
  • Lithium
    • This medication is targeting Akt and GSK3 (both of which that were mentioned above) to regulate the overall Wnt signaling pathway.

Links and/or images:

https://pubmed.ncbi.nlm.nih.gov/23379509/

https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216848/

An Overview of Addiction

Drug addiction, also known as substance use disorder, is the inability to control impulses regarding drug-seeking and drug-using behavior. Addiction can result from knowingly overindulging in a substance, from being administered drugs in a clinical setting that are inherently addictive, and everywhere in between. Regardless of the cause of these behaviors, the brain is affected in a very similar way. Some drugs are addictive by their very nature, such as nicotine or opiates, and some are not addictive but the repeated administration can result in a dependency, leading to the same addictive outcome.

What are Gateway Drugs?

Gateway drugs are drugs that encourage the user to experiment with stronger, more dangerous drugs; not by the way of “I smoke cigarettes so now I want to try heroin” but by the way that these drugs are so addictive that they make the brain more susceptible to becoming addicted to new substances. This is best explained by the gateway-drug effect, which explains that the repeated use of particular psychoactive drugs increases the chance of using and becoming addicted to other substances, usually stronger and more dangerous, by altering neural connectivity throughout the brain (particularly the nucleus accumbens (NAc) and ventral tegmental area (VTA)). Some of these drugs include tobacco, alcohol, and marijuana, but the list is difficult to completely define.

Animal Models of Multi-Drug Addiction

While the gateway-drug effect has been shown in humans, it has been the most easily studied in animal models. Studies show that repeated THC injections in mice increase the self-administration of morphine, heroin, and nicotine. Nicotine addiction in mice was found to increase cocaine consumption and drug-seeking behavior compared to non-addicted mice. Alcohol was found to increase drug-seeking behaviors for cocaine and decreased the average time needed to become addicted to the substance. In all of these experiments, profound changes were seen in the reward regions of the brain in very similar ways, regardless of drug class.

Neurophysiology of Drug Addiction

Figure 1 – Reward, Plasticity, and Behaviors associated with Chronic Drug Use

Drugs become addictive largely by their effects on dopamine signaling in the NAc and VTA, which play overarching roles in reward, motivation, and addictive behaviors due to the large deposits of dopaminergic neurons in these areas. In the context of gateway drugs, even a single administration of a substance can increase dopamine release in the NAc and VTA, which can have immediate, long-term effects on both the affected neuron and synapse (Figure 1). Figure 1 shows that repeated drug exposure increases DA activity and encourages AMPA receptor migration to the post-synaptic domain and decreases NMDA receptor density, which ultimately increases long-term potentiation (LTP). By having a very high amount of AMPA receptors on the postsynaptic cell, it is much more sensitive to excitation, which strengthens the connections between the two neurons.

Conclusions

Ultimately, this explains that repeated drug use strengthens the connections between neurons in the NAc and VTA which makes it very difficult to stop the use of an addictive drug. Gateway drugs do exactly this. By becoming addicted to this small collection of substances, the brain can be altered for years, even permanently, encouraging the use of stronger, dangerous drugs. This is not to say that smoking marijuana or having a cocktail now and then will lead to drug addiction, but it is important to understand the risks of chronic use.

Sources

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898681/
2. https://www.mayoclinic.org/diseases-conditions/drug-addiction/symptoms-causes/syc-20365112
3. https://www.sciencedirect.com/science/article/pii/S0092867415009629
4. https://bluefirewilderness.com/blog/gateway-drugs-nipping-drug-use-in-the-bud/