title: Regulation of cocaine-induced reinstatement by group II metabotropic glutamate receptors in the ventral tegmental area.
abstract: BACKGROUND
  A high rate of relapse is a daunting challenge facing clinical treatment of cocaine addiction. Recent studies have shown that drugs of abuse enhance glutamate neurotransmission in dopamine neurons in the ventral tegmental area (VTA) and such enhancement may contribute to the risk of relapse.
  
  
  OBJECTIVE
  Given the important role of group II metabotropic glutamate receptors (mGluR2/3s) in regulating glutamate release from the glutamatergic terminals, this study aimed to test whether activation of mGluR2/3s in the VTA can inhibit cocaine-induced reinstatement of cocaine-seeking behavior, a model of relapse to drug-seeking behavior.
  
  
  METHODS
  Rats were trained to self-administer intravenous cocaine (0.25 mg/infusion) under a modified fixed-ratio 5 schedule. After rats reached the training criteria, they went through extinction training to extinguish cocaine-seeking behavior. Then the dose-response effects of a selective mGluR2/3 agonist LY 379268 microinjected into the VTA on cocaine-induced reinstatement of cocaine-seeking behavior were assessed.
  
  
  RESULTS
  LY 379268 (0.032-0.1 μg/side) dose-dependently decreased cocaine-induced reinstatement. The effect could not be fully attributed to diffusion of the drug to the neighboring substantia nigra or to motor impairment. Interestingly, LY 379268 has a less potent effect on cocaine-induced reinstatement than on sucrose-induced reinstatement of sucrose-seeking behavior.
  
  
  CONCLUSIONS
  Our data support the idea that glutamate release in the VTA is critically involved in cocaine-induced reinstatement and indicate that loss of mGluR2/3-mediated regulation of glutamate release in the VTA may critically contribute to the risk of relapse.
authors: Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Crowe 115, Memphis, TN 38163, USA.
authors: Lianyi
authors: L
authors: Lu
authors: Yueqiang
authors: Y
authors: Xue
authors: Jeffery D
authors: JD
authors: Steketee
authors: George V
authors: GV
authors: Rebec
authors: Wenlin
authors: W
authors: Sun
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D012008:Recurrence; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D003042:Cocaine