title: Reinstatement of cocaine seeking in 129X1/SvJ mice: effects of cocaine priming, cocaine cues and food deprivation.
abstract: OBJECTIVE
  The mechanisms underlying relapse to cocaine seeking induced by exposure to priming cocaine injections, cues associated with cocaine self-administration and environmental stressors have been studied in rats. Here we describe a reinstatement method for studying relapse to cocaine seeking in mice, a suitable species for studying the effect of genetic manipulations such as gene knockout or gene over-expression on compulsive drug use.
  
  
  METHODS
  Male mice of the 129X1/SvJ strain were trained for 14-16 days to self-administer cocaine (0.75 mg/kg/infusion; 4 h/day; fixed-ratio-1 schedule of reinforcement; infusions were paired with a light-tone compound cue). Next, the lever-pressing behavior was extinguished by removing the cocaine syringes in the presence (Exps. 1 and 3) or absence (Exp. 2) of the cocaine cue. Subsequently, tests for reinstatement were conducted after exposure to priming injections of cocaine (0, 1.5, 3.0 and 6.0 mg/kg, IV; Exp. 1), response-contingent presentations of the cocaine-associated cue (Exp. 2), or food deprivation stress (1 and 22 h; Exp. 3).
  
  
  RESULTS
  The effect of cocaine priming on reinstatement was modest and was only observed at the highest dose tested. On the other hand, reinstatement of cocaine seeking was observed following exposure to the cocaine-associated cue and food deprivation stress.
  
  
  CONCLUSIONS
  The present data suggest that factors contributing to relapse to drugs can be studied in the reinstatement model using the common 129X1/SvJ mouse inbred strain.
authors.affiliation: Behavioral Neuroscience Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Highfield
authors.forename: Andy N
authors.initials: AN
authors.lastname: Mead
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Grimm
authors.forename: Beatriz A
authors.initials: BA
authors.lastname: Rocha
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000523:psychology*; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D008297:Male; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012646:Self Administration / Q000523:psychology
chemical_list: D003042:Cocaine