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Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced reinstatement of cocaine-seeking behavior in rats

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Abstract

Rationale

The functional integrity of the dorsal hippocampus (DH) is necessary for drug context-induced reinstatement of cocaine seeking. However, the neuropharmacological mechanisms of this phenomenon are poorly understood.

Objectives

Given the known significance of group I metabotropic glutamate receptors (mGluRs), including the mGluR1 subtype, in drug-induced behaviors, the present study was designed to evaluate the contribution of mGluR1s in the DH to drug context-induced reinstatement of extinguished cocaine-seeking behavior.

Methods

Sprague–Dawley rats were trained to lever press for unsignaled cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a distinctly different environmental context (extinction context). Using a counterbalanced partial within-subjects testing design, rats were re-exposed to the cocaine-paired context or the extinction context while cocaine-seeking behavior (nonreinforced active lever pressing) was assessed. Prior to each test session, rats received bilateral microinfusions of the highly potent mGluR1-selective antagonist JNJ16259685 (0.6, 30, or 120 pg/0.5 μl per hemisphere) or vehicle into the DH or the overlying somatosensory cortex trunk region (SStr; anatomical control).

Results

Intra-DH, but not intra-SStr, JNJ16259685 infusions dose dependently attenuated drug context-induced reinstatement of cocaine seeking relative to vehicle treatment, without attenuating instrumental behavior in the extinction context, general motor activity, or food-reinforced instrumental behavior in control experiments.

Conclusions

Stimulation of mGluR1s in the DH is necessary for incentive motivational and/or memory processes that contribute to drug context-induced cocaine-seeking behavior. These findings indicate that the mGluR1 is an interesting target from an addiction treatment perspective.

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Acknowledgments

The authors thank Stephanie Kaszycki, KaiCee Ponds, Andrew Hamlet, Jennifer Shurney, and Chandler Sours for excellent technical assistance. The authors do not have any conflicts of interest to disclose. This work was supported by National Institute on Drug Abuse (NIDA) grant R01 DA017673, a NIDA R01 grant supplement to promote diversity in health-related research (DA017673-S1), a University of North Carolina at Chapel Hill Junior Faculty Development Award, and the Mason and Linda Stephenson Faculty Award.

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  1. Department of Psychology, University of North Carolina, CB# 3270, Davie Hall, Chapel Hill, NC, USA

    Xiaohu Xie, Donna R. Ramirez, Heather C. Lasseter & Rita A. Fuchs

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  1. Xiaohu Xie
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  2. Donna R. Ramirez
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  3. Heather C. Lasseter
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Correspondence to Rita A. Fuchs.

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Xie, X., Ramirez, D.R., Lasseter, H.C. et al. Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced reinstatement of cocaine-seeking behavior in rats. Psychopharmacology 208, 1–11 (2010). https://doi.org/10.1007/s00213-009-1700-7

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  • DOI: https://doi.org/10.1007/s00213-009-1700-7

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