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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 9, 2007; DOI: 10.1124/jpet.107.130625

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Received for publication August 22, 2007.
Revised November 7, 2007.
Accepted for publication November 8, 2007.

Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rhesus monkeys

Jun-Xu Li 1, Kenner C Rice 2, Charles P. France 3*

1 the University of Texas Health Science Center at San Antonio 2 NIDA/NIH 3 University of Texas Health Science Center

* Address correspondence to: E-mail: france{at}uthscsa.edu

Abstract

Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/kg (s.c.) of DOM and vehicle after an average of 116 (range=85-166) sessions while responding under a fixed ratio (FR) 5 schedule of stimulus shock termination. Increasing doses of DOM occasioned increased responding on the drug lever with the training dose occasioning DOM-lever responding for up to 2 hrs. The serotonin (5-HT)2A/2C receptor antagonists ritanserin and ketanserin, the 5-HT2A receptor antagonist MDL100907 and its stereoisomer MDL100009, but not haloperidol, completely blocked the discriminative stimulus effects of DOM. Quipazine as well as several drugs with hallucinogenic activity in humans, including (+)lysergic acid diethylamide (LSD), (-)DOM and 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), occasioned DOM-lever responding. The kappa opioid receptor agonists U-50488 and salvinorin A (a hallucinogen) did not exert DOM-like effects and neither did ketamine, phencyclidine, amphetamine, methamphetamine, cocaine, morphine, yohimbine, fenfluramine, 8-OH-DPAT or N-0434. These data confirm in non-human primates a prominent role for 5-HT2A receptors in the discriminative stimulus effects of some drugs with hallucinogenic activity in humans. The failure of another drug with hallucinogenic activity (salvinorin A) to substitute for DOM indicates that different classes of hallucinogens exert qualitatively different discriminative stimulus effects in non-humans.


Key words: DOM, LSD, drug discrimination, hallucinogen, rhesus monkey, serotonin




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