title: Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.
abstract: BACKGROUND
  Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior.
  
  
  OBJECTIVE
  In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior.
  
  
  METHODS
  Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session.
  
  
  RESULTS
  Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior.
  
  
  CONCLUSIONS
  Together, these data suggest that chronic ethanol exposure drives impairments in the ability to use reward-paired cues to adaptively regulate behavior and that mGluR2/3 receptors represent a therapeutic target for restoration of these deficits in behavioral control in the alcoholic.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Barker
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lench
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 29425, USA. chandj@musc.edu.
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects; D000437:Alcoholism / Q000523:psychology*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003259:Consummatory Behavior / Q000187:drug effects; D003463:Cues; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011597:Psychomotor Performance / Q000187:drug effects; D018091:Receptors, AMPA / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012201:Reward; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C118218:LY 379268; D018091:Receptors, AMPA; D014966:Xanthenes; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Alcohol; Cue-mediated behavior; Metabotropic glutamate receptors