The ability of various receptor agonists and antagonists were used to characterize the discriminative stimulus effects of ethanol. Antagonists at the 5HT3 receptor/ion complex were found to block the discriminative stimulus properties of ethanol in pigeons given orally administered ethanol. These data confirm data from electrophysiological studies which demonstrated that ethanol was potentiating the effects of serotonin at the 5-HT3 receptor. The discriminative stimulus properties of ethanol were blocked in a dose dependent manner by two antagonists acting at the 5-HT3 receptor. Increasing the dose of ethanol could overcome this blockade. The specificity of the blockade by 5-HT3 antagonists was tested using antagonists of the 5-HT2 receptor and a dopaminergic antagonist. Neither of these compounds blocked ethanol's discrimination. The ability of the 5-HT3 antagonists to block other behavioral effects of ethanol was tested using an hypnotic dose of ethanol (measuring loss of righting reflex), and a moderate dose of ethanol (measuring motor coordination). The 5-HT3 antagonists did not block either of these effects of ethanol, suggesting that the action of ethanol at the 5-HT3 receptor is not related to the motor effects of ethanol. The role of the 5-HT3 receptor in mediating the reinforcing effects of ethanol was also tested in a preparation using a rhesus monkey self-administering ethanol intravenously.
