Abstract

Rats were trained to discriminate between intraperitoneal injections of 0.16 mg/kg of d-lysergic acid diethylamide ( d-LSD) and injections of saline in the two-bar (FR 10) food-reinforced drug discrimination procedure. The gradient for responses to LSD was established following pretreatment with saline or one of five doses of pirenperone. It was found that pretreatment with pirenperone caused a parallel shift to the right of the dose-effect curve of LSD. The magnitude of this shift was related to the dose of pirenperone, 0.006 mg/kg of the drug causing a 2-fold shift. A direct linear plot revealed that the curve fitting the data points passed through the origin, but that it was curvilinear rather than linear. The data did not, therefore, accomodate the requirements for reversible, competitive interaction. This finding is discussed in terms of the mixed agonist/antagonist activity of LSD that may occur at binding sites for 5-HT 1 and 5-HT 2 in the rat brain.

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