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Alcohol‐induced reinforcement: Dopamine and 5‐HT 3 receptor interactions in animals and humans
Author(s) -
Johnson Bankole A.,
Cowen Philip J.
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430300308
Subject(s) - nucleus accumbens , ventral tegmental area , dopamine , dopaminergic , psychology , neuroscience , pharmacology , dopamine receptor d2 , dopamine receptor , medicine
Alcohol abuse is a major health problem worldwide. Whatever the treatment goal, be it abstinence or “controlled” drinking, the outcome from both pharmacological and nonbiological treatments remains disappointing. Behavioural experiments in animals have suggested that the reinforcing properties of alcohol, like other drugs of abuse, are critical to drug‐seeking behaviour. Dopaminergic fibres running from the ventral tegmental area to the nucleus accumbens may play a central role in mediating the reinforcing effects of drugs of abuse including alcohol. Thus, alcohol increases extracellular levels of dopamine in the nucleus accumbens and dopamine receptor antagonists decrease alcohol consumption in a number of behavioural paradigms. A recently described subtype of serotonin (5‐HT) receptor, the 5‐HT 3 receptor, appears to modulate the effects of alcohol on dopamine release in the nucleus accumbens. In rodents, 5‐HT 3 receptor antagonists inhibit alcohol‐induced dopamine release in the nucleus accumbens. Further, in behavioural studies, 5‐HT 3 receptor blockade decreases alcohol consumption in a free‐choice paradigm. In humans, reinforcement is difficult to measure directly. Nevertheless, the pleasurable subjective effects of alcohol are important behavioural correlates of the reinforcement process. Our preliminary findings in humans suggest that the 5‐HT 3 receptor antagonist, ondansetron, can attenuate some of the pleasurable effects of a small dose of alcohol including the subjective desire to drink. We speculate, although we have no direct evidence for this at present, that in humans this effect could also be due to a blockade of alcohol‐induced dopamine release in the nucleus accumbens as has been demonstrated in animals. Further studies with clinical populations are required to assess the effects of 5‐HT 3 receptor antagonists on drinking behaviour and to explore their potential in the management of alcohol abuse. © 1993 wiley‐Liss, Inc.