Serotonin and drugs of abuse

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The role of 5-HT in the control of alcohol intake has received considerable attention following the discovery that 5-HT reuptake inhibitors reduce alcohol intake in alcohol dependent rats. Similar effects have been found for intracerebroventricularly administered 5-HT or its precursor 5-HTP. Regarding the type of 5-HT receptor involved, there is experimental evidence that the 5-HT1A partial agonists buspirone and gepirone are effective. Differences were found between the effects of the 5-HT3 antagonist ondansetron and the 5-HT2A/5-HT2c antagonist ritanserin. Thus the 5-HT3 antagonist ondansetron reduces alcohol intake without affecting the alcohol preference of rats, while ritanserin reduces both the alcohol preference and intake. This suggests that, at least in rats, different populations of 5-HT receptors may be involved in alcohol intake and preference.

Regarding other types of drugs of abuse, the 5-HT3 antagonist MDL 72222 has been shown to block place preference conditioning induced in rodents by morphine or nicotine without affecting the preference for amphetamine. It is possible that these effects of 5-HT3 antagonists are associated with the reduction in dopamine release as it is well established that the rewarding effects of many drugs of abuse are due to increased dopaminergic activity in limbic regions. On the strength of the experimental findings, it has been proposed that 5-HT3 antagonists might be useful in treating drug abuse in man. Only appropriate placebo-controlled studies of 5-HT3 antagonists will clarify the therapeutic value of such agents in different types of drug abuse.

A further discussion of the pharmacological properties of alcohol and other drugs of abuse is given in Chapter 15.

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