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Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats
Author(s) -
Besheer Joyce,
Faccidomo Sara,
Grondin Julie J. M.,
Hodge Clyde W.
Publication year - 2008
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00570.x
Subject(s) - metabotropic glutamate receptor 5 , antagonist , metabotropic glutamate receptor 1 , metabotropic glutamate receptor , ethanol , metabotropic receptor , self administration , chemistry , alcohol , pharmacology , glutamate receptor , antagonism , medicine , biochemistry , receptor
Background: Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self‐administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement. Methods: Alcohol‐preferring (P) rats were trained to self‐administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self‐administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance. Results: The mGluR1 antagonist, 3,4‐dihydro‐2H‐pyrano[2,3]b quinolin‐7‐yl ( cis ‐4‐methoxycyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6‐methyl‐2‐(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose‐dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity. Conclusions: Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self‐administer ethanol.