CB1 cannabinoid receptor modulates 3,4-methylenedioxymethamphetamine acute responses and reinforcement.

Full Abstract

BACKGROUND:
3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endocannabinoid system is involved in the addictive processes induced by different drugs of abuse. However, the role of this system in the pharmacological effects of MDMA has not yet been clarified.

METHODS:
Locomotion, body temperature, and anxiogenic-like responses were evaluated after acute MDMA administration in CB(1) cannabinoid receptor 1 knockout mice. Additionally, MDMA rewarding properties were investigated in the place conditioning and the intravenous self-administration paradigms. Extracellular levels of dopamine (DA) in the nucleus accumbens were also analyzed after a single administration of MDMA by in vivo microdialysis.

RESULTS:
Acute MDMA administration increased locomotor activity, body temperature, and anxiogenic-like responses in wild-type mice, but these responses were lower or abolished in knockout animals. 3,4-Methylenedioxymethamphetamine produced similar conditioned place preference and increased dopamine extracellular levels in the nucleus accumbens in both genotypes. Nevertheless, CB(1) knockout mice failed to self-administer MDMA at any of the doses used.

CONCLUSIONS:
These results indicate that CB(1) cannabinoid receptors play an important role in the acute prototypical effects of MDMA and are essential in the acquisition of an operant behavior to self-administer this drug.

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Author information

Author/s: Touriño, Clara (C); Ledent, Catherine (C); Maldonado, Rafael (R); Valverde, Olga (O);

Affiliation: Grup de Recerca de Neurobiologia del Comportament (GRNC), Departament de Ciències de Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Biological psychiatry (Biol Psychiatry), published in United States. (Language: eng)

Reference: 2008-Jun; vol 63 (issue 11) : pp 1030-8

Dates: Created 2008/05/16; Completed 2008/07/16;

PMID: 17950256, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

3,4-Methylenedioxyamphetamine - pharmacology
Analysis of Variance
Animals
Anxiety - chemically induced
Behavior, Animal - drug effects
Body Temperature - drug effects
Conditioning, Operant - drug effects
Dopamine - metabolism
Dose-Response Relationship, Drug
Drug Administration Routes

Hallucinogens - pharmacology
Male
Mice
Mice, Knockout
Microdialysis - methods
Motor Activity - drug effects
Nucleus Accumbens - drug effects; metabolism
Receptor, Cannabinoid, CB1 - deficiency; physiology
Reinforcement (Psychology)
Self Administration

Associated Chemicals: Hallucinogens (0) ; Receptor, Cannabinoid, CB1 (0) ; 3,4-Methylenedioxyamphetamine (4764-17-4) ; Dopamine (51-61-6)

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