Apparent pA2 analysis of 5‐HT2A receptor antagonists in rhesus monkeys discriminating DOM

Abstract

Discriminative stimulus effects of 1‐(2,5‐dimethoxy‐4‐methylphenyl)‐2‐aminopropane (DOM) have been well characterized in rats and less so in other species. This study used Schild analysis and a cumulative‐dosing procedure to systematically examine the receptor mechanisms that mediate the discriminative stimulus effects of DOM in rhesus monkeys. Four rhesus monkeys discriminated between 0.32 mg/kg (s.c.) DOM and vehicle while responding under an FR 5 schedule of stimulus shock termination. DOM and the 5‐HT1A/5‐HT2A receptor agonist dipropyltryptamine (DPT) increased responding on the DOM lever. M100907 (0.001–0.01 mg/kg), ketanserin (0.01–0.1 mg/kg) and ritanserin (0.01–0.1 mg/kg) shifted the dose‐response curves of DOM and DPT rightward in a parallel manner. Schild analyses were consistent with a simple, competitive interaction and yielded a pA2 value of 8.5 for M100907 with DOM or DPT; a pA2 value of 7.7 was obtained for ketanserin and for ritanserin with DOM or DPT. These results confirm the role of 5‐HT2A receptors in the discriminative stimulus effects of DOM and extend the use of Schild analysis to this discrimination procedure in monkeys, thereby providing the basis for future studies investigating the role of particular 5‐HT receptor subtypes in the behavioral effects of DOM and related drugs. CPF is supported by RCA DA17918.