title: Inhibiting glycine transporter-1 facilitates cocaine-cue extinction and attenuates reacquisition of cocaine-seeking behavior.
abstract: BACKGROUND
  Combining extinction training with cognitive-enhancing pharmacotherapy represents a novel strategy for improving the efficacy of exposure therapy for drug relapse prevention. We investigated if the selective glycine transporter-1 (GlyT-1) inhibitor RO4543338 could facilitate extinction of cocaine-conditioned responses and attenuate reacquisition of cocaine-seeking behavior.
  
  
  METHODS
  Rats were trained to self-administer cocaine (0.3mg/kg), which was associated with a 2-s light cue under a second-order schedule of i.v. drug injection. Rats received vehicle, 30 or 45mg/kg of RO4543338 prior to three 1-h extinction-training sessions spaced at weekly intervals. Responses were extinguished by substituting saline for cocaine while maintaining response-contingent cue presentations. Reacquisition of cocaine-seeking behavior during self-administration sessions began 1 week after the last extinction session. Control experiments were conducted under conditions that precluded explicit extinction of cocaine-conditioned responses.
  
  
  RESULTS
  Compared to vehicle, 30 and 45mg/kg RO4543338 significantly decreased responding early in extinction training and during subsequent reacquisition sessions. The latter effect persisted for at least five sessions. In control studies, reacquisition of cocaine-seeking behavior was not altered when RO4543338 was administered either prior to weekly self-administration control sessions or prior to weekly control sessions in which cocaine and cues were omitted and the levers retracted.
  
  
  CONCLUSIONS
  As the GlyT-1 inhibitor facilitated cocaine-cue extinction learning and attenuated subsequent reacquisition of cocaine-seeking behavior, this class of compounds may have utility as a pharmacological adjunct to cocaine-cue exposure therapy in addicts.
authors: Department of Psychology, Boston University, 64 Cummington Street, Boston, MA 02215, USA.
authors: Bríd Á
authors: BÁ
authors: Nic Dhonnchadha
authors: Emmanuel
authors: E
authors: Pinard
authors: Daniela
authors: D
authors: Alberati
authors: Joseph G
authors: JG
authors: Wettstein
authors: Roger D
authors: RD
authors: Spealman
authors: Kathleen M
authors: KM
authors: Kantak
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D048289:Imidazolidines / Q000037:antagonists & inhibitors*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013141:Spiro Compounds / Q000037:antagonists & inhibitors*
chemical_list: C573643:1-(4-fluorophenyl)-8-(2-(4-fluorophenyl)-2-hydroxycyclohexyl)-1,3,8-triazaspiro(4.5)decan-4-one; D018765:Dopamine Uptake Inhibitors; D050487:Glycine Plasma Membrane Transport Proteins; D048289:Imidazolidines; D013141:Spiro Compounds; D003042:Cocaine