Regulation of Motivation to Self‐Administer Ethanol by mGluR5 in Alcohol‐Preferring (P) Rats
- 21 December 2007
- journal article
- Published by Wiley in Alcohol: Clinical and Experimental Research
- Vol. 32 (2), 209-221
- https://doi.org/10.1111/j.1530-0277.2007.00570.x
Abstract
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.Keywords
This publication has 48 references indexed in Scilit:
- Delayed Access to Alcohol Accelerates Self‐Administration of Alcohol on a Progressive Ratio ScheduleBasic & Clinical Pharmacology & Toxicology, 2006
- The γ‐Aminobutyric Acid‐B Receptor Agonist Baclofen Attenuates Responding for Ethanol in Ethanol‐Dependent RatsAlcohol: Clinical and Experimental Research, 2006
- Analgesic effects of mGlu1 and mGlu5 receptor antagonists in the rat formalin testNeuropharmacology, 2006
- Neuroprotective potential of group I metabotropic glutamate receptor antagonists in two ischemic modelsNeurochemistry International, 2006
- Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesisNeuropharmacology, 2005
- mGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor CoordinationScience, 2000
- Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brainJournal of Comparative Neurology, 1995
- Effects of intraaccumbens injections of dopamine agonists and antagonists on sucrose and sucrose-ethanol reinforced respondingPharmacology Biochemistry and Behavior, 1994
- GABA and Nucleus Accumbens Glutamate Neurotransmission Modulate Ethanol Self‐Administration in RatsaAnnals of the New York Academy of Sciences, 1992
- Initiation of Ethanol Reinforcement using a Sucrose‐Substitution Procedure in Food‐ and Water‐Sated RatsAlcohol: Clinical and Experimental Research, 1986