Role of serotonin in the discriminative stimulus properties of mescaline

Pharmacology, Biochemistry and Behavior
Vol 3 (No. 3) May-Jun 1975; 429-435
by Ronald G. Browne; Beng T. Ho


Trained male Sprague-Dawley rats to discriminate intraperitoneally administered mescaline from saline in a 2-lever operant chamber for food reinforcement. Reward was contingent upon responses made greater than 15 sec apart on the appropriate lever paired with either drug or saline administration. Following the establishment of discriminative response control by mescaline, Ss were tested for stimulus generalization produced by mescaline after (a) blockade of peripheral and central serotonin (5-hydroxytryptamine, 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). Results show that all 3 central 5-HT antagonists greatly reduced the discriminability of mescaline, while the peripheral antagonist xylamidine tosylate was without effect. These agents at the doses employed did not affect the discriminability of saline. Depletion of 5-HT with PCPA potentiated the effects of a subthreshold dose of mescaline and slightly reduced the discriminability of saline. Results indicate that mescaline produces its discriminative stimulus properties by directly stimulating central serotonergic receptors.




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