Role of serotonin in the discriminative stimulus properties of mescaline

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.

Study at a glance

Abstract

Rats were trained to discriminate intraperitoneally administered mescaline from saline in a two-lever operant chamber for food reinforcement. Reward was contingent upon responses made greater than 15 sec apart (DRL-15) on the appropriate lever paired with either drug or saline administration. Following the establishment of discriminative response control by mescaline, the animals were tested for stimulus generalization produced by mescaline after: (a) blockade of periphreral and central serotonin (5-HT) receptors with cinanserin, methysergide, or cyproheptadine; (b) blockade of peripheral 5-HT receptors with xylamidine tosylate; and (c) depletion of brain 5-HT with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA). The results show that all three central 5-HT antagonists greatly reduced the discriminability of mescaline while the peripheral antagonist, xylamidine tosylate, was without effect. Furthermore, these agents at the doses employed did not effect the discriminability of saline. Depletion of 5-HT with PCPA potentiated the effects of a sub-threshold dose of mescaline and slightly reduced the discriminability of saline. The results indicate that mescaline produces its discriminative stimulus properties by directly stimulating central serotonergic receptors.