title: D-cycloserine facilitates extinction of cocaine self-administration in C57 mice.
abstract: BACKGROUND
  Cocaine is a highly addictive drug of abuse for which there are currently no medications. In rats and mice d-cycloserine (DCS), a partial NMDA agonist, accelerates extinction of cocaine seeking behavior. Since cues delay extinction here, we evaluated the effects d-cycloserine in extinction with and without the presence of cues.
  
  
  METHODS
  Two doses of DCS (15 and 30 mg/kg) were studied in C57 mice. Mice self-administered cocaine (1 mg/kg) for 2 weeks and then underwent a 20-day extinction period where DCS was administered i.p. immediately following each daily session. Extinction was conducted in some mice with the presence of cocaine-paired cues; while others were in the absence of these cues.
  
  
  RESULTS
  DCS treated mice (either dose) showed significantly reduced lever pressing during extinction with cue exposures when compared with vehicle treated mice. Without cues, animals showed much lower levels of lever pressing but the differences between vehicle and DCS were not significant.
  
  
  CONCLUSIONS
  DCS accelerated extinction with the presence of cues, but there were no differences on extinction without cues as compared with vehicle. These findings are consistent with DCS disrupting the memory process associated with the cues. Since drug cues are significantly involved in relapse, these findings support research to assess the therapeutic potential of DCS in cocaine addiction.
authors.affiliation: Laboratory of Neuroimaging, NIAAA, NIH, Bethesda, USA. thanos@bnl.gov
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Mike
authors.initials: M
authors.lastname: Subrize
authors.forename: Wendy
authors.initials: W
authors.lastname: Lui
authors.forename: Zachary
authors.initials: Z
authors.lastname: Puca
authors.forename: Mala
authors.initials: M
authors.lastname: Ananth
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D003523:Cycloserine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005108:Extinction, Psychological / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000819:agonists*; D012646:Self Administration / Q000379:methods; D013237:Stereoisomerism
chemical_list: D018765:Dopamine Uptake Inhibitors; D016202:N-Methylaspartate; D003523:Cycloserine; D003042:Cocaine