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

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

  1. Jatelka
    Journal of Pharmacology and Experimental Therapeutics 2008 Dec 19. [Epub ahead of print]

    Li JX (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Rice KC (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), France CP (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).

    Discriminative stimulus effects of the serotonin (5-HT) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) have been studied in rats and more recently in rhesus monkeys. This study examined DOM, 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and dipropyltryptamine (DPT) alone and in combination with three antagonists (MDL100907, ketanserin and ritanserin) to identify the 5-HT receptor subtype(s) that mediates the discriminative stimulus effects of these 5-HT receptor agonists. Four adult rhesus monkeys discriminated between 0.32 mg/kg (s.c.) DOM and vehicle while responding under a fixed ratio 5 schedule of stimulus shock termination. DOM, 2C-T-7 and DPT dose-dependently increased responding on the DOM-associated lever. MDL100907 (0.001-0.01 mg/kg), ketanserin (0.01-0.1 mg/kg), and ritanserin (0.01-0.1 mg/kg) each shifted the dose-response curves of DOM, 2C-T-7 and DPT rightward in a parallel manner. Schild analysis of each drug combination was consistent with a simple, competitive, and reversible interaction. Similar apparent affinity (pA2) values were obtained for MDL100907 in combination with DOM (8.61), 2C-T-7 (8.58), or DPT (8.50), for ketanserin with DOM (7.67), 2C-T-7 (7.75), or DPT (7.71), and for ritanserin with DOM (7.65), 2C-T-7 (7.75), or DPT (7.65). Potency of antagonists in this study was correlated with binding affinity at 5-HT2A receptors and not at 5-HT2C or alpha1 adrenergic receptors. This study used Schild analysis to examine receptor mechanisms mediating the discriminative stimulus effects of hallucinogenic drugs acting at 5-HT receptors; results provide quantitative evidence for the predominant if not exclusive role of 5-HT2A receptors in the discriminative stimulus effects of DOM, 2C-T-7, and DPT in rhesus monkeys.