Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats.

Full Abstract

RATIONALE:
Nucleus accumbens glutamate transmission has been implicated in drug-seeking behavior, but the involvement of glutamate receptor subtypes in drug seeking maintained by drug-associated cues has not been fully investigated.

OBJECTIVE:
This study examined the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate, N-methyl-D-aspartate (NMDA) and mGlu5 receptor blockade in the nucleus accumbens core on cue-induced reinstatement of cocaine seeking.

METHOD:
Wistar rats were trained to self-administer cocaine and associate a compound stimulus (light and tone) with the drug under an FR4(FR5:S) second-order schedule of reinforcement. After extinction, during which neither cocaine nor the compound stimulus was available, responding was reinstated by contingent presentations of the compound stimulus. The effects of the intra-accumbal AMPA/kainate receptor antagonist 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX; 0, 0.01, and 0.03 microg/side), the NMDA antagonist D-2-amino-5-phosphonopentanoate (D-AP5; 0, 1, and 2 microg/side), and the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP; 0, 0.5, and 1 microg/side) on reinstatement were examined in a within-subjects design.

RESULTS:
CNQX and D-AP5 attenuated cue-induced reinstatement of cocaine seeking dose-dependently. MPEP, however, decreased cocaine seeking only relative to baseline because also the saline vehicle included in the within-subjects series of injections decreased responding, possibly reflecting conditioned anhedonic effects of MPEP. In additional experiments, none of the antagonists attenuated locomotor activity or responding for sucrose pellets.

CONCLUSIONS:
The results suggest that cue-induced reinstatement of cocaine seeking after a period of withdrawal from cocaine is sensitive to AMPA/kainate and NMDA receptor antagonism in the nucleus accumbens core and give further evidence for the role of the accumbal glutamate transmission in modulation of drug-seeking behavior.

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Author information

Author/s: Bäckström, Pia (P); Hyytiä, Petri (P);

Affiliation: Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.

Journal and publication information

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

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

Reference: 2007-Jul; vol 192 (issue 4) : pp 571-80

Dates: Created 2007/06/01; Completed 2007/08/06;

PMID: 17347848, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

2-Amino-5-phosphonovalerate - pharmacology
6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology
Animals
Cocaine - administration & dosage
Cocaine-Related Disorders - physiopathology; psychology
Conditioning (Psychology) - drug effects
Cues
Dopamine Uptake Inhibitors - administration & dosage
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists - pharmacology
Extinction, Psychological - drug effects

Extinction, Psychological - drug effects
Male
Motor Activity - drug effects
Nucleus Accumbens - drug effects; physiopathology
Pyridines - pharmacology
Rats
Rats, Wistar
Receptors, Kainic Acid - antagonists & inhibitors; physiology
Receptors, Metabotropic Glutamate - antagonists & inhibitors; physiology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; physiology
Self Administration

Associated Chemicals: 6-methyl-2-(phenylethynyl)pyridine (0) ; Dopamine Uptake Inhibitors (0) ; Excitatory Amino Acid Antagonists (0) ; Pyridines (0) ; Receptors, Kainic Acid (0) ; Receptors, Metabotropic Glutamate (0) ; Receptors, N-Methyl-D-Aspartate (0) ; metabotropic glutamate receptor 5 (0) ; 6-Cyano-7-nitroquinoxaline-2,3-dione (115066-14-3) ; Cocaine (50-36-2) ; 2-Amino-5-phosphonovalerate (76726-92-6)

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