Estimating the relative reinforcing strength of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine.

Full Abstract

RATIONALE:
(+/-)3,4-Methylenedioxymethamphetamine (MDMA) is an analog of methamphetamine (MA) and a drug of abuse. MA, MDMA, and its isomers release monoamine neurotransmitters with varying selectivities and would, therefore, be predicted to vary in their relative strength as reinforcers.

OBJECTIVES:
This study compared self-administration of MA, MDMA, and its isomers using a progressive-ratio schedule in rhesus monkeys.

METHODS:
Rhesus monkeys [n = 6, MA and MDMA; n = 5, (+)-MDMA and (-)-MDMA] were prepared with chronic i.v. catheters and allowed to self-administer cocaine or saline in daily baseline sessions. When responding was stable, MA (0.006-0.1 mg/kg per injection), MDMA (0.025-0.8 mg/kg injection), (+)-MDMA (0.025-0.8 mg/kg per injection), or (-)-MDMA (0.05-0.8 mg/kg per injection) was made available in test sessions.

RESULTS:
MA, MDMA, and (+)-MDMA functioned as positive reinforcers in all monkeys with a potency relationship of MA > (+)-MDMA > (+/-)-MDMA. Two of five monkeys took (-)-MDMA above saline levels. Dose-response relationships were biphasic for MA and (+/-)-MDMA, and asymptotic for (+)-MDMA. In terms of maximum number of injection per session, a measure of relative reinforcing strength, the order was MA > (+)-MDMA = (+/-)-MDMA > (-)-MDMA.

CONCLUSIONS:
MDMA and (+)-MDMA were consistent positive reinforcers, but weaker than MA, whereas (-)-MDMA was, at best, a weak reinforcer in some monkeys. The reinforcing strength of MDMA appears to derive primarily from (+)-MDMA. Because MDMA and its isomers have been shown to have relatively higher serotonin to dopamine releasing potency, these data support the hypothesis that increasing 5-HT releasing potency relative to DA is associated with weaker reinforcing effects.

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Author information

Author/s: Wang, Zhixia (Z); Woolverton, William L (WL);

Affiliation: Department of Psychiatry, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.

Grants: DA-10352 (Agency:NIDA NIH HHS) ; DA-15343 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: Psychopharmacology (Psychopharmacology (Berl)), published in Germany. (Language: eng)

Reference: 2007-Jan; vol 189 (issue 4) : pp 483-8

Dates: Created 2006/11/22; Completed 2007/03/02; Revised 2007/12/03;

PMID: 17063335, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Behavior, Animal - drug effects
Brain - drug effects; metabolism
Central Nervous System Stimulants - administration & dosage
Cocaine - administration & dosage
Dopamine - metabolism
Dose-Response Relationship, Drug
Isomerism
Macaca mulatta

Male
Methamphetamine - administration & dosage
N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; chemistry
Reinforcement (Psychology)
Reinforcement Schedule
Self Administration
Serotonin - metabolism
Serotonin Agents - administration & dosage; chemistry
Structure-Activity Relationship

Associated Chemicals: Central Nervous System Stimulants (0) ; Serotonin Agents (0) ; N-Methyl-3,4-methylenedioxyamphetamine (42542-10-9) ; Cocaine (50-36-2) ; Serotonin (50-67-9) ; Dopamine (51-61-6) ; Methamphetamine (537-46-2)

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