Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline

In order to further evaluate the extent to which particular 5-HT receptor subtypes (5-HT₁, 5-HT₂) might be involved in the behavioral effects of hallucinogenic drugs, rats were trained to discriminate mescaline (10 mg/kg i.p.) from saline and were given substitution (generalization) and combination (antagonism) tests with putatively selective serotonergic and related neuroactive compounds. The mescaline cue generalized to relatively high doses of the 5-HT₂ agonists, 2,5-dimethoxy-4-methylamphetamine (DOM), LSD and psilocybin; the extent of generalization to 5-HT₁ agonists (8-hydroxy-2-[diethylamino]tetralin (8-OHDPAT), RU-24969 and 8-hydroxy-2-[di-n-propylamino]tetralin (TFMPP) was unclear. Combinations of the training drug and sufficiently high doses of 5-HT₂ antagonists (ketanserin, LY-53857, pirenperone) were followed by saline-lever responding; less selective central 5-HT (metergoline), and DA (SCH-23390, haloperidol) antagonists, did not block the mescaline cue. These data suggest that 5-HT₂ receptors are involved in the stimulus properties of mescaline.