During lecture, we learned that alcohol consumption is
responsible for about 85,000 deaths annually in the United States. Roughly 32% of traffic deaths involve alcohol
use, it is the third leading cause of preventable death, and a third of all
violent crimes in this country involve alcohol consumption. The article that I read discussed the type of
neurons in the brain that could be correlated with both nicotine and ethanol
activation. These are the nicotinic
acetylcholine receptors which are widely expressed in the Ventral Tegmental
Area of the brain and has distinct connections projecting to both parts of the
nucleus accumbens, the prefrontal cortex, and the hippocampus. Dopaminergic and GABAergic VTA neurons contain
various subtypes of nAch receptors, each with different pharmacological and
biological properties.
Ethanol has been found to act on GABA, NMDA, 5-HT3, and nACh receptors, and through the modulation of nACh receptors may contribute to the mechanism of action of ethanol and the co-abuse of nicotine and alcohol. As discussed in class, the reward system of the nucleus accumbens is correlated with an increase in dopamine release and widely associated with drugs of abuse. According to the article, the specific role of dopamine release in reward is uncertain; however, ethanol and nicotine release of dopamine in the NAc is vital for dependence to occur.
Ethanol is not a direct agonist at nACHRs, it potentiates or inhibits them depending on the subtype, specifically the α4 nAChRs in the VTA dopaminergic neurons. The article also had an interesting section concerning mecamylamine, a potential nAChR antagonist which has been shown to reduce ethanol consumption and block alcohol-induced dopamine release in the nucleus accumbens. However, this antagonist blocks almost all subtypes of nAChRs, so additional studies have been pursued to pinpoint specific subtypes responsible for ethanol's mechanism of action.
Currently three FDA approved medications exist for treatment of alcoholism; Disulfiram, Naltrexone, and Acamprosate, but they aren't effective enough, with only 20-30% of treated patients responding to them. Already, studies have been producing new drugs including Varenicline, an α4β2 agonist; Sazetidine-A, an α4β2 nAChR desensitizer and partial agonist; Lobeline, an antagonist with high affinity for α4β2 and α3β2 nACh receptors, and Cytisine, an agonist for β2 and β4 nACh receptors. Humans may have heritable polymorphisms within nicotinic acetocholine receptor subunit genes that predispose them to higher risks of alcoholic disorders and ethanol/nicotine co-abuse. Future studies should definitely be performed regarding neuronal nACH receptors throughout the brain because they are potential sites for the remedy of both alcohol and nicotine dependence.
Ethanol has been found to act on GABA, NMDA, 5-HT3, and nACh receptors, and through the modulation of nACh receptors may contribute to the mechanism of action of ethanol and the co-abuse of nicotine and alcohol. As discussed in class, the reward system of the nucleus accumbens is correlated with an increase in dopamine release and widely associated with drugs of abuse. According to the article, the specific role of dopamine release in reward is uncertain; however, ethanol and nicotine release of dopamine in the NAc is vital for dependence to occur.
Ethanol is not a direct agonist at nACHRs, it potentiates or inhibits them depending on the subtype, specifically the α4 nAChRs in the VTA dopaminergic neurons. The article also had an interesting section concerning mecamylamine, a potential nAChR antagonist which has been shown to reduce ethanol consumption and block alcohol-induced dopamine release in the nucleus accumbens. However, this antagonist blocks almost all subtypes of nAChRs, so additional studies have been pursued to pinpoint specific subtypes responsible for ethanol's mechanism of action.
Currently three FDA approved medications exist for treatment of alcoholism; Disulfiram, Naltrexone, and Acamprosate, but they aren't effective enough, with only 20-30% of treated patients responding to them. Already, studies have been producing new drugs including Varenicline, an α4β2 agonist; Sazetidine-A, an α4β2 nAChR desensitizer and partial agonist; Lobeline, an antagonist with high affinity for α4β2 and α3β2 nACh receptors, and Cytisine, an agonist for β2 and β4 nACh receptors. Humans may have heritable polymorphisms within nicotinic acetocholine receptor subunit genes that predispose them to higher risks of alcoholic disorders and ethanol/nicotine co-abuse. Future studies should definitely be performed regarding neuronal nACH receptors throughout the brain because they are potential sites for the remedy of both alcohol and nicotine dependence.
Link to
Article:
http://www.ncbi.nlm.nih.gov.ezaccess.libraries.psu.edu/pmc/articles/PMC3639424/pdf/fpsyt-04-00029.pdf
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