title: Attenuation of reinstatement of methamphetamine-, sucrose-, and food-seeking behavior in rats by fenobam, a metabotropic glutamate receptor 5 negative allosteric modulator.
abstract: BACKGROUND
  Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction.
  
  
  OBJECTIVE
  Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior.
  
  
  METHODS
  Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10, or 15 mg/kg intraperitoneal) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking.
  
  
  RESULTS
  Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested.
  
  
  CONCLUSIONS
  The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to nonspecific suppression of general appetitive behaviors.
authors: Department of Psychology, Arizona State University, PO Box 871104, 950 S McAllister Avenue, Tempe, AZ 85287, USA.
authors: Lucas R
authors: LR
authors: Watterson
authors: Peter R
authors: PR
authors: Kufahl
authors: Natali E
authors: NE
authors: Nemirovsky
authors: Kaveish
authors: K
authors: Sewalia
authors: Lauren E
authors: LE
authors: Hood
authors: M Foster
authors: MF
authors: Olive
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage*
chemical_list: C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C032794:fenobam; D008694:Methamphetamine; D013395:Sucrose