title: Environmental condition alters amphetamine self-administration: role of the MGluR₅ receptor and schedule of reinforcement.
abstract: BACKGROUND
  Evidence suggests that differential rearing influences the function of a receptor subtype critical for maintaining glutamate homeostasis. Maintaining homeostatic glutamatergic function may be an important protector against drug abuse.
  
  
  OBJECTIVE
  This study sought to determine if differential rearing influences the function of a receptor critical for glutamate homeostasis, which could in turn affect rates of amphetamine self-administration.
  
  
  METHODS
  Rats were assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After rearing for 30 days, rats were trained to lever press for sucrose reinforcement before the implantation of indwelling jugular catheters. After reaching stable responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before self-administration sessions. Following fixed-ratio (FR-1) testing, rats were administered identical doses of MTEP on a progressive-ratio (PR) reinforcement schedule.
  
  
  RESULTS
  MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03 mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0 mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0 mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR results also revealed that IC rats not treated with MTEP were more motivated to self-administer the higher dose of amphetamine.
  
  
  CONCLUSIONS
  These results suggest that the mGlu5 receptor mediates differences in drug-taking behavior among differentially reared rats. Isolation also decreased sensitivity to MTEP, suggesting that environmental factors alter glutamate homeostasis which subsequently affects sensitivity and motivation to self-administer amphetamine.
authors.affiliation: Department of Psychological Sciences, Kansas State University, 492 Bluemont Hall, Manhattan, KS, 66506, USA, david23@ksu.edu.
authors.forename: D L
authors.initials: DL
authors.lastname: Arndt
authors.forename: K C
authors.initials: KC
authors.lastname: Johns
authors.forename: Z K
authors.initials: ZK
authors.lastname: Dietz
authors.forename: M E
authors.initials: ME
authors.lastname: Cain
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D019969:Amphetamine-Related Disorders / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004777:Environment; D008297:Male; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000502:physiology*; D012055:Reinforcement Schedule; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D013395:Sucrose; D000661:Amphetamine