Abstract
(+)-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”; “X”; “E”) is a popular recreational amphetamine analog that produces a unique set of effects in humans and animals. MDMA use is often associated with dance parties called “raves”, but its use has increased in all segments of society and around the world. Like amphetamine, MDMA elicits hyperactivity when administered to rodents. Unlike amphetamine, which has effects mediated by the release of dopamine (DA) from nerve terminals, MDMA-induced hyperactivity is thought to be dependent upon the release of 5-hydroxtryptamine (5-HT). However, MDMA elicits large increases in synaptic concentrations of both DA and 5-HT, and the interaction between these neurotransmitters may account for the unique characteristics of the drug. Comparisons between MDMA, the selective DA releaser amphetamine, and the selective 5-HT releaser fenfluramine are used in the present discussion to highlight the ability of MDMA to model the locomotor activation induced by the interaction of DA and 5-HT. Furthermore, this review summarizes evidence to suggest that the influence of 5-HT receptors on behavioral function is dependent upon the specific neurochemical environment evoked by a given drug, specifically discussed here with regard to the interaction between 5-HT and DA systems.
Footnotes
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Send reprint requests to: Kathryn A. Cunningham, Ph.D., Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031. E-mail:cunningham{at}utmb.edu
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The work was supported in part by the National Institute on Drug Abuse Grants DA 006511, DA 00260, and DA 07287. This review was presented by M.G.B. in partial fulfillment of the requirements for the Ph.D. degree to the Graduate School of Biomedical Sciences at the University of Texas Medical Branch.
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We apologize to those scientists whose research in the areas of 5-HT and MDMA neuropharmacology was not referenced due to the citation limits.
- Abbreviations:
- (+)-MDMA
- (+)-3,4-methylenedioxymethamphetamine
- 5-HT
- 5-hydroxytryptamine
- DA
- dopamine
- DOI
- (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
- GR 127935
- [2′-methyl-4′-(5-methyl-(1,2,4)oxadiazol-3-yl)-biphenyl-4-carboxylic acid (4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl-amide)
- M100907
- [R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol]
- NAc
- nucleus accumbens
- RU 24969
- [5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole]
- SB 206553
- [N-3-pyridinyl-3,5-dihydro-5-methylbenzo(1,2-b:4,5-b′)dipyrrole-1(2H) carboxamide]
- VTA
- ventral tegmental area
- SERT
- 5-HT transporter
- DAT
- DA transporter
- R
- receptor(s)
- SN
- substantia nigra
- GABA
- γ-aminobutyric acid
- MCPP
- m-chlorophenylpiperazine
- Received October 24, 2000.
- Accepted February 5, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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3,4-Methylenedioxymethamphetamine (MDMA) as a Unique Model of Serotonin Receptor Function and Serotonin-Dopamine Interactions
