title: The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats.
abstract: BACKGROUND
  Recent research indicates that blockade of mGluR5 modifies the reinforcing properties of ethanol.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Schroeder
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Clyde W
authors.initials: CW
authors.lastname: Hodge
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000431:Ethanol; C121465:6-methyl-2-(phenylethynyl)pyridine; D011493:Protein Kinase C
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