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Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats.
Psychopharmacology (Berl) 2007; 192(4):571-80P

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.

Authors+Show Affiliations

Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17347848

Citation

Bäckström, Pia, and Petri Hyytiä. "Involvement of AMPA/kainate, NMDA, and mGlu5 Receptors in the Nucleus Accumbens Core in Cue-induced Reinstatement of Cocaine Seeking in Rats." Psychopharmacology, vol. 192, no. 4, 2007, pp. 571-80.
Bäckström P, Hyytiä P. Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl). 2007;192(4):571-80.
Bäckström, P., & Hyytiä, P. (2007). Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats. Psychopharmacology, 192(4), pp. 571-80.
Bäckström P, Hyytiä P. Involvement of AMPA/kainate, NMDA, and mGlu5 Receptors in the Nucleus Accumbens Core in Cue-induced Reinstatement of Cocaine Seeking in Rats. Psychopharmacology (Berl). 2007;192(4):571-80. PubMed PMID: 17347848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats. AU - Bäckström,Pia, AU - Hyytiä,Petri, Y1 - 2007/03/09/ PY - 2006/11/24/received PY - 2007/02/19/accepted PY - 2007/3/10/pubmed PY - 2007/8/7/medline PY - 2007/3/10/entrez SP - 571 EP - 80 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 192 IS - 4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/17347848/Involvement_of_AMPA/kainate_NMDA_and_mGlu5_receptors_in_the_nucleus_accumbens_core_in_cue_induced_reinstatement_of_cocaine_seeking_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-007-0753-8 DB - PRIME DP - Unbound Medicine ER -