title: The group II metabotropic glutamate receptor agonist, LY379268, decreases methamphetamine self-administration in rats.
abstract: BACKGROUND
  Given the problems associated with the escalation in methamphetamine (METH) use, the identification of more effective treatment strategies is essential. Group II metabotropic glutamate receptors (mGluRs) have been suggested to be a novel therapeutic target for psychostimulant addiction. We sought to test the ability of the selective group II mGluR agonist LY379268 to reduce METH self-administration in rats.
  
  
  METHODS
  Rats were trained to self-administer METH on a progressive ratio (PR) schedule. Animals were then switched to fixed ratio responding and given daily extended access (6 h/day) to METH self-administration for 14 days. Rats were then re-tested on the PR schedule. The effect of LY379268 on METH-reinforced PR responding was determined before and after 14 days of extended access. To test for non-specific effects, a separate group of animals received LY379268 prior to a sucrose pellet-reinforced PR schedule.
  
  
  RESULTS
  Animals escalated their daily intake of METH during extended access. PR responding did not change as a function of extended access. LY379268 significantly attenuated METH reinforced responding, both before and after extended access. The degree of attenuation did not change as a function of extended access. LY379268 had no effect on sucrose pellet-reinforced responding at any dose.
  
  
  CONCLUSIONS
  LY379268 selectively reduced the motivation to self-administer METH. In contrast to data with other compounds, the sensitivity to the effects of LY379268 did not change following extended access to METH self-administration. Group II mGluR agonists, therefore, may represent a relatively new class of compounds for the development of pharmacotherapies for METH addiction.
authors: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, United States.
authors: Jordan T
authors: JT
authors: Crawford
authors: David C S
authors: DC
authors: Roberts
authors: Thomas J R
authors: TJ
authors: Beveridge
mesh_terms: D000596:Amino Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D012646:Self Administration
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D008694:Methamphetamine
keywords: Extended-access; LY369268; Methamphetamine; Self-administration
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