Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats
Article first published online: 21 DEC 2007
Alcoholism: Clinical and Experimental Research
Volume 32, Issue 2, pages 209–221, February 2008
How to Cite
Besheer, J., Faccidomo, S., Grondin, J. J. M. and Hodge, C. W. (2008), Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats. Alcoholism: Clinical and Experimental Research, 32: 209–221. doi: 10.1111/j.1530-0277.2007.00570.x
- Issue published online: 21 DEC 2007
- Article first published online: 21 DEC 2007
- Received for publication April 23, 2007; accepted October 17, 2007.
- Ethanol Self-Administration;
- Progressive Ratio;
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.