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The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats

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Abstract

Rationale

Recent research indicates that blockade of mGluR5 modifies the reinforcing properties of ethanol.

Objectives

The present studies examined the effects of mGluR5 receptor blockade in a genetic model of high ethanol intake, the alcohol-preferring (P) rat, on the maintenance of operant ethanol self-administration. In addition, we determined the effect of 2-methyl-6-(phenylethyl)-pyridine (MPEP) on the repeated alcohol deprivation effect.

Methods

Twelve male (P) rats were trained in experimental sessions to self-administer 10% w/v ethanol via a sucrose-fading procedure. After the establishment of operant ethanol self-administration, subjects were treated with various metabotropic glutamate receptor (mGluR) subtype antagonists immediately prior to experimental sessions: the mGluR5 antagonist MPEP (1, 3, and 10 mg/kg); the mGluR2–3 antagonist LY-341495 (1, 3, and 10 mg/kg); and the mGluR1 antagonist CPCCOEt (1, 3, and 10 mg/kg). After determining the role of mGluR5 in the maintenance of operant ethanol self-administration, we examined the role of this receptor in relapse following repeated periods of alcohol deprivation by depriving subjects of ethanol exposure for three 2-week deprivation periods.

Results

The mGluR5 antagonist MPEP dose-dependently decreased operant ethanol self-administration. In addition, rats that received saline immediately prior to repeated alcohol deprivation sessions self-administered ethanol at increasing levels that were above those achieved in the last operant-conditioning session prior to the initial 2-week deprivation period. This repeated alcohol deprivation effect was prevented in subjects pretreated with MPEP (10 mg/kg).

Conclusions

These findings suggest that mGluR5 receptors may modulate both the maintenance of operant ethanol self-administration and abstinence-induced increases in ethanol intake.

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Acknowledgements

This work was supported by the National Institute on Alcoholism Abuse and Alcoholism.

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Authors and Affiliations

  1. Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building, CB #7178, Chapel Hill, NC, 27599, USA

    Jason P. Schroeder, David H. Overstreet & Clyde W. Hodge

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  1. Jason P. Schroeder
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  2. David H. Overstreet
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  3. Clyde W. Hodge
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Correspondence to Clyde W. Hodge.

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Schroeder, J.P., Overstreet, D.H. & Hodge, C.W. The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology 179, 262–270 (2005). https://doi.org/10.1007/s00213-005-2175-9

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