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

Sep 10, 2008Pharmacology, biochemistry, and behavior

How 8-OH-DPAT and MDMA change the recognition of the hallucinogen DOM in rats

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Abstract

Co-administration of MDMA with low doses of DOM resulted in enhanced DOM-appropriate responding in rats.

The 5-HT1A serotonin receptor agonist (+/-)8-OH DPAT increases the effects of the hallucinogen DOM.
The stimulus-enhancing effects of 8-OH DPAT are primarily attributed to its R(+) isomer.
The effects of 8-OH DPAT and its R(+) isomer can be blocked by the 5-HT1A receptor antagonist NAN-190.
Both 8-OH DPAT and its isomers can substitute in rats trained to recognize MDMA.
This study provides the first evidence that MDMA can enhance the stimulus effects of a classical hallucinogen.

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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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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

Abstract

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