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Role of protein kinase C epsilon (PKCɛ) in the reduction of ethanol reinforcement due to mGluR5 antagonism in the nucleus accumbens shell

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Abstract

Rationale

The type 5 metabotropic glutamate receptor (mGluR5) and the epsilon isoform of protein kinase C (PKCɛ) regulate ethanol intake, and we have previously demonstrated that mGluR5 receptor antagonism reduces ethanol consumption via a PKCɛ-dependent mechanism.

Objectives

We explored the potential neuroanatomical substrates of regulation of ethanol reinforcement by this mGluR5-PKCɛ signaling pathway by infusing selective inhibitors of these proteins into the shell or core region of the nucleus accumbens (NAc).

Methods

Male Wistar rats were trained to self-administer ethanol intravenously and received intra-NAc infusions of vehicle or the selective mGluR5 antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) alone and in combination with a PKCɛ translocation inhibitor (ɛV1–2) or a scrambled control peptide (sɛV1–2). The effects of intra-NAc MTEP on food-reinforced responding and open-field locomotor activity were also determined.

Results

MTEP (1 μg/μl) had no effect on ethanol or food reinforcement or locomotor activity when infused into either region. MTEP (3 μg/μl) reduced ethanol reinforcement when infused into the NAc shell but not the core, and this effect was reversed by ɛV1–2 (1 μg/μl) but not sɛV1–2 (1 μg/μl). In both regions, this concentration of MTEP did not alter food-reinforced responding or locomotor activity, and infusion of ɛV1–2 alone did not alter ethanol reinforcement. MTEP (10 μg/μl) reduced locomotor activity when infused into the shell; therefore, this concentration was not further tested on responding for ethanol or food.

Conclusions

Blockade of mGluR5 receptors in the NAc shell reduces ethanol reinforcement via a PKCɛ-dependent mechanism.

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Acknowledgements

This work was supported by National Institutes of Health grant AA013852 (MFO) and an Institutional Training Grant AA007474 (JTG). The authors wish to thank Ms. Noreen Watson for technical assistance in conducting these studies. The authors have no conflicts of interest to declare.

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  1. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, MSC 861, Charleston, SC, 29425, USA

    Justin T. Gass & M. Foster Olive

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  1. Justin T. Gass
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Correspondence to M. Foster Olive.

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Gass, J.T., Olive, M.F. Role of protein kinase C epsilon (PKCɛ) in the reduction of ethanol reinforcement due to mGluR5 antagonism in the nucleus accumbens shell. Psychopharmacology 204, 587–597 (2009). https://doi.org/10.1007/s00213-009-1490-y

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