Alcoholism is one of the serious addiction problems that we are facing today. Data state that alcoholism affect some 14 million people in the United States alone, costing US$ 184 billion a year. (Newton &Messing, 2006) Why are some of us addicted to alcohol and why is alcohol a part of our society? Alcohol plays a big role as a mediating agent among social interactions today. The amount, frequency and subsequent magnitude of impact on the individuals vary as the reasons for drinking varies. In this blog, I will focus on the addictive potential, withdrawal symptoms of alcohol as well as the current therapeutic targets.
Dopamine is the major neurotransmitter in the brain that induces feelings of reward and reinforcement. Alcohol increases the neural firing of dopamine neurons in the ventral tegmental region of the brain. This activation in turn causes increases increase release of dopamine in the nucleus accumbens, a region in the brain that is rich in dopaminergic neurons. Along this signal transduction cascade, this dopamine activates a particular type of neurons called DARPP-32 which increases the level of glutamatergic NMDA receptors which counteracts the inhibition of receptor function by alcohol of the neurons. Hence, DARPP-32 neurons are important in facilitating rewarding feelings of alcohol. Alcohol also induces addictive effects through the mesolimbic pathway which involves amygdala, a brain region that regulates emotions, in the brain which is involved in dopamine-induced pleasurable feelings. Alcohol induces increase release of opioids (e.g. beta endorphins) in the brain and these opioids inhibit the inhibition of dopamine neurons by GABA (gamma-amino-butyric-acid) which is a major inhibitory system of neural actions in the brain. Hence, alcohol induces addiction similar to that of nicotine and opioid drugs.
The most challenging aspect of treating alcohol and drug addiction is the relapsing course of these disorders. Although substitution therapies for nicotine and opioid dependence have proven to be relatively effective, there is a need for new pharmacotherapies designed to decrease the frequency and severity of relapse. NMDA receptor antagonists are one of the targets for treatment of alcohol addiction since blocking the action of the NMDA receptor can block the increase dopamine release and dopamine-related feelings of reward. MK-801 is one of the widely used NMDA receptor antagonists in treatment of alcoholism.
According to the article ‘Treatment of Alcohol Withdrawal’ by Myrick.et.al, withdrawal symptoms of alcohol include headache, tremor, sweating, agitation, anxiety and irritability, nausea and vomiting, heightened sensitivity to light and sound, disorientation, difficulty concentrating, and, in more serious cases, transient hallucinations.. Patients with alcohol withdrawal should be subject to a physical examination, with particular emphasis on detecting conditions such as irregular heartbeat (i.e., arrhythmia), inadequate heart function (i.e., congestive heart failure), liver disease (e.g., alcoholic hepatitis), pancreatic disease (i.e., alcoholic pancreatitis), infectious diseases (e.g., tuberculosis), bleeding within the digestive system, and nervous system impairment. Vital signs (e.g., heartbeat and blood pressure) should be stabilized and disturbances of water and nutritional balances corrected. (Myrick.et.al, 1998)
Alcohol : Why are we addicted to it?
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