Rats trained to distinguish mescaline from saline in a two-lever task showed that blocking central serotonin receptors with cinanserin, methysergide, or cyproheptadine greatly reduced their ability to recognize mescaline, while blocking only peripheral serotonin receptors with xylamidine tosylate had no effect. Depleting brain serotonin with PCPA made a low dose of mescaline more detectable and slightly impaired saline discrimination. These findings suggest mescaline produces its distinctive internal effects by directly activating serotonin receptors in the brain.
Rats trained to discriminate between a mescaline (25 mg/kg) and a saline state in a two-lever operant chamber showed that neither the metabolites 3,4,5-trimethoxyphenylethanol (TMPE), 3,4,5-trimethoxyphenylacetaldehyde (TMPA), nor N-acetylmescaline generalized to the mescaline cue, regardless of pretreatment with aldehyde dehydrogenase or amine oxidase inhibitors. Both inhibitors enhanced the effects of mescaline itself. The findings suggest that a metabolite is not responsible for the interoceptive stimulus produced by mescaline.