Serotonin and drugs of abuse

Serotonin and drugs of abuse
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 MDL72222
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.