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Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats

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.
- University of North Carolina at Chapel Hill United States
- UNC Lineberger Comprehensive Cancer Center United States
- UNC Lineberger Comprehensive Cancer Center United States
- Center for Alcohol Studies Thailand
- Center for Alcohol Studies Thailand
Male, Motivation, Reinforcement Schedule, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Receptor, Metabotropic Glutamate 5, Motor Activity, Receptors, Metabotropic Glutamate, Choice Behavior, Rats, Alcoholism, Animals
Male, Motivation, Reinforcement Schedule, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Receptor, Metabotropic Glutamate 5, Motor Activity, Receptors, Metabotropic Glutamate, Choice Behavior, Rats, Alcoholism, Animals
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