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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.
Pharmacol Biochem Behav. 2009 Jan; 91(3):385-92.PB

Abstract

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.

Authors+Show Affiliations

Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18778728

Citation

Khorana, Nantaka, et al. "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." Pharmacology, Biochemistry, and Behavior, vol. 91, no. 3, 2009, pp. 385-92.
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;91(3):385-92.
Khorana, N., Young, R., & Glennon, R. A. (2009). 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. Pharmacology, Biochemistry, and Behavior, 91(3), 385-92. https://doi.org/10.1016/j.pbb.2008.08.013
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;91(3):385-92. PubMed PMID: 18778728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Khorana,Nantaka, AU - Young,Richard, AU - Glennon,Richard A, Y1 - 2008/08/17/ PY - 2007/12/10/received PY - 2008/08/04/revised PY - 2008/08/09/accepted PY - 2008/9/10/pubmed PY - 2009/4/3/medline PY - 2008/9/10/entrez SP - 385 EP - 92 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 91 IS - 3 N2 - 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. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/18778728/Effect_of_8_hydroxy_2__NN_di_n_propylamino_tetralin_and_MDMA_on_the_discriminative_stimulus_effects_of_the_classical_hallucinogen_DOM_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(08)00286-4 DB - PRIME DP - Unbound Medicine ER -