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Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice.
J Pharmacol Exp Ther. 2009 Nov; 331(2):717-23.JP

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse "ecstasy." The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(-)-enantiomers tend to have hallucinogen-like effects, whereas S(+)-enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(-)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine/norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-hydroxytryptamine (5-HT)(2A) agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT(2A) agonist/monoamine reuptake inhibitor N,N-dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA-treated animals but did not substitute for the R(-)-MDMA cue. 2C-T-7 fully substituted in the R(-)-MDMA-trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but whereas cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(-)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further our understanding of the complex nature of the interoceptive effects of MDMA.

Authors+Show Affiliations

Emory University, Neuroscience Graduate Program, Atlanta, Georgia, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19684254

Citation

Murnane, K S., et al. "Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA Trained Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 331, no. 2, 2009, pp. 717-23.
Murnane KS, Murai N, Howell LL, et al. Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice. J Pharmacol Exp Ther. 2009;331(2):717-23.
Murnane, K. S., Murai, N., Howell, L. L., & Fantegrossi, W. E. (2009). Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice. The Journal of Pharmacology and Experimental Therapeutics, 331(2), 717-23. https://doi.org/10.1124/jpet.109.156174
Murnane KS, et al. Discriminative Stimulus Effects of Psychostimulants and Hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA Trained Mice. J Pharmacol Exp Ther. 2009;331(2):717-23. PubMed PMID: 19684254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice. AU - Murnane,K S, AU - Murai,N, AU - Howell,L L, AU - Fantegrossi,W E, Y1 - 2009/08/14/ PY - 2009/8/18/entrez PY - 2009/8/18/pubmed PY - 2009/12/16/medline SP - 717 EP - 23 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 331 IS - 2 N2 - 3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse "ecstasy." The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(-)-enantiomers tend to have hallucinogen-like effects, whereas S(+)-enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(-)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine/norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-hydroxytryptamine (5-HT)(2A) agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT(2A) agonist/monoamine reuptake inhibitor N,N-dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA-treated animals but did not substitute for the R(-)-MDMA cue. 2C-T-7 fully substituted in the R(-)-MDMA-trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but whereas cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(-)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice and further our understanding of the complex nature of the interoceptive effects of MDMA. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/19684254/Discriminative_stimulus_effects_of_psychostimulants_and_hallucinogens_in_S_+__34_methylenedioxymethamphetamine__MDMA__and_R____MDMA_trained_mice_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=19684254 DB - PRIME DP - Unbound Medicine ER -