Abstract
The development of a new animal model for alcoholism is described. Objective, biologic criteria for an animal model were established which did not conflict with either the criteria for the alcohol dependence syndrome of ICD-10 or the criteria for the alcohol dependence in DSM-IV. The 5-hydroxytryptamine (5-HT) system has long been thought to play a role at several steps in the cycle of alcohol abuse and dependence. Agents that increase serotonergic tone have shown promising results in assisting with recovery from alcoholism, whereas the 5-HT3 antagonist ondansetron was found effective in a clinical trial. Dopamine in the nucleus accumbens is thought to be involved in alcoholism via a ‘‘common reward pathway’’, perhaps as the final common denominater. The role of serotonin as a main regulator of dopamine in the nucleus accumbens is emphasized. Activation of 5-HT3 receptors depolarizes the membrane, causing neurotransmitter release, primarily dopamine in the nucleus accumbens. 5-HT3 antagonists can counteract some of the events in the common reward pathway and ‘‘break’’ some of the effects of ethanol in both initial drinking and during abstinence. Tropisetron reduces ethanol consumption in alcoholpreferring rats and increases it in abstainers. Tropisetron significantly reduced ethanol intake in Alcohol-Preferring Rats, whereas it increased ethanol intake in Low-Alcohol-Preferring Rats. These findings draw attention to the possibility of tropisetron having a more complex action than merely 5-HT3 receptor blockade. The effect of tropisetron applied by re6erse microdialysis into the6entral tegmental area on ethanol consumption in rats. This study examined the effect of tropisetron applied directly into the ventral tegmental area, by reverse microdialysis, using rats selected on the basis of a free-choice model for natural alcohol preference. Although not significant in this study, there was a tendency for tropisetron to attenuate the rats’ preference for alcohol when applied by this route. The effect of alcohol and tropisetron on dopamine le6els in the nucleus accumbens. This study examined the effect of a single dose of ethanol on the dopamine level in the nucleus accumbens and also the combined effect of single doses of tropisetron and
Published Version
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