Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-3,4-methylenedioxymethamphetamine (MDMA) and R(-)-MDMA trained mice.
Kevin S. Murnane, Naoki Murai, Leonard L. Howell, William E Fantegrossi
Journal of Pharmacology and Experimental Therapeutics November 1, 2009 DOI: 10.1124/jpet.109.156174 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Qualitative Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | S(+)-amphetamine cocaine 2C-T-7 DPT |
| Topics | MDMA |
| Keywords | Psychoactive effects Drug mimicry Pharmacology |
| Citations | 34 |
| Key points | The two enantiomers of MDMA produce qualitatively different discriminative stimulus effects in mice, with S(+)-MDMA showing stimulant-like properties and R(-)-MDMA showing hallucinogen-like properties. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 16
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs Natural Product Reports 2014
- Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents. Behavioural Pharmacology August 1, 2017
- Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants. Neuropsychopharmacology December 1, 2024
- Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder. Psychedelic Medicine September 1, 2023
and 11 more in the library
Cites 13
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in mice and rats. Psychopharmacology September 1, 2005
- Differential effects of intravenous R,S‐(±)‐3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy) and its S(+)‐ and R(−)‐enantiomers on dopamine transmission and extracellular signal regulated kinase phosphorylation (pERK) in the rat nucleus accumbens shell and core Journal of Neurochemistry January 22, 2007
- Assessment of the discriminative stimulus effects of the optical isomers of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) Behavioural Pharmacology April 1, 1995
- Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and its enantiomers in mice: pharmacokinetic considerations. Journal of Pharmacology and Experimental Therapeutics June 2009
and 8 more in the library