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The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs.

David J. Mokler, K W Stoudt, Richard H. Rech

Pharmacology, biochemistry, and behavior May 1985 DOI: 10.1016/0091-3057(85)90512-x (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational study Peer reviewed
Population Rats responding under a fixed-ratio 40 schedule of reinforcement
Interventions LSD DMT mescaline DOM quipazine lisuride pirenperone
Key findings Pirenperone shifted the dose-response curves for phenethylamine hallucinogens (mescaline, DOM) significantly to the right and to a greater degree than those for indolealkylamine hallucinogens (LSD, DMT), and antagonized quipazine similarly to the phenethylamines, but did not significantly shift lisuride's dose-response pattern. The authors suggest that the behavioral disruption induced by these hallucinogens and quipazine relates at least in part to an effect on 5HT2 receptors, while lisuride's effects do not involve a significant interaction at the 5HT2 receptor.

Abstract

Indolealkylamine and phenethylamine hallucinogens disrupted responding maintained under a fixed-ratio 40 (FR-40) schedule of reinforcement. LSD, DMT, mescaline and DOM produced dose-dependent decreases in number of reinforcers and increases in 10-sec periods of non-responding (pause-intervals). The 5HT agonist quipazine, as well as the LSD congener lisuride, altered response patterns in a similar manner. The effects of these drugs were examined after pretreatment with pirenperone, an antagonist with specificity toward the 5HT2 receptor with reference to the 5HT1 receptor. The dose-response curves for the phenethylamine hallucinogens were shifted significantly to the right and to a greater degree than were those for the indolealkylamine hallucinogens. Pirenperone also antagonized the effects of quipazine to a degree similar to that observed with the phenethylamine-type hallucinogens. Pirenperone did not significantly shift the dose-response pattern to lisuride. These data suggest that the behavioral disruption induced by these hallucinogens and quipazine relates at least in part to an effect on 5HT2 receptors, while the effects of lisuride do not involve a significant interaction at the 5HT2 receptor.