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Khorana N, Young R, Glennon RA: Effect of 8-hydroxy-2-(N,N-di-n-propylamino) tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats. Pharmacol Biochem Behav. 2009 Jan;91(3):385-92. Epub 2008 Aug 17.
Co-administration of the 5-HT1A serotonin receptor agonist (+/-) 8-hydroxy-2-(N,N-di-n-propylamino) tetralin [(+/-) 8-OH DPAT] enhances the discriminative stimulus effects of the classical hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats. In the present investigation, using Sprague-Dawley rats trained to discriminate DOM (1.0 mg/kg) from saline vehicle under a VI-15 s schedule of reinforcement, it was shown that the stimulus-enhancing actions of 8-OH DPAT are related more to its R (+)-isomer than to its S (-)-enantiomer, and that the (+/-)- and R (+) 8-OH DPAT-induced effects are antagonized by the 5-HT1A receptor antagonist NAN-190. (+/-) 8-OH DPAT and its isomers substitute in rats trained to discriminate the designer drug N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; methylenedioxymethamphetamine) from vehicle indicating some similarity of effect. On this basis, it was hypothesized that MDMA might be capable of enhancing the DOM stimulus. Co-administration of MDMA with low (i.e., 0.1 and 0.3 mg/kg) doses of DOM resulted in greater DOM-appropriate responding than engendered by administration of DOM alone. As such, the present findings are the first to demonstrate an MDMA-induced enhancing effect on the discriminative stimulus actions of a classical hallucinogen. The results also suggest that a 5-HT1A serotonin receptor mechanism might contribute to this phenomenon. |
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