title: Medial prefrontal cannabinoid CB1 receptors modulate consolidation and extinction of cocaine-associated memory in mice.
abstract: BACKGROUND
  Cannabinoid CB1 receptors are implicated in various forms of learning and memory, including acquisition and reinstatement of cocaine-associated memory. However, roles of CB1 receptors in consolidation and extinction processes of cocaine-associated memory and the brain areas potentially involved remain unknown.
  
  
  OBJECTIVE
  This study examined the effect of rimonabant, a CB1 receptor antagonist, administered systemically or directly into the medial prefrontal cortex (mPFC) on memory consolidation and extinction of cocaine-induced conditioned place preference (CPP).
  
  
  METHODS
  Male C57BL/6J mice were trained to acquire cocaine-induced CPP. Rimonabant (0.1-3 mg/kg, i.p. or 1.5 μg bilaterally in the mPFC) or vehicle was administered either immediately after each CPP training (consolidation) or forced extinction (extinction) trial. Cocaine-induced CPP was tested after training, extinction, or cocaine priming.
  
  
  RESULTS
  Systemic or intra-mPFC administration of rimonabant impaired consolidation of CPP induced by a high dose (20 or 40 mg/kg) of cocaine but facilitated that induced by a low dose (2.5, 5, or 10 mg/kg). Moreover, systemic or intra-mPFC administration of rimonabant enhanced extinction of CPP memory induced by a high-dose (20 mg/kg) cocaine.
  
  
  CONCLUSIONS
  Our results suggest that antagonism of CB1 receptors in the mPFC bidirectionally modulates consolidation but facilitates extinction of cocaine-induced CPP memory. Therefore, CB1 receptor blockade with the concomitant extinction behavioral procedure may hint important therapeutic intervention strategies for the heavy cocaine addicts in a clinical setting.
authors.affiliation: Cannabinoid Signaling Laboratory, Department of Psychology, National Cheng Kung University, 1 University Rd., Tainan, 70101, Taiwan, shujungh@mail.ncku.edu.tw.
authors.forename: Sherry Shu-Jung
authors.initials: SS
authors.lastname: Hu
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Liu
authors.forename: Lung
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant
chemical_list: D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D003042:Cocaine; D000077285:Rimonabant