title: NMDA receptor glycine modulatory site in the ventral tegmental area regulates the acquisition, retrieval, and reconsolidation of cocaine reward memory.
abstract: OBJECTIVE
  Accumulating clinical and preclinical studies have shown that the memories of the rewarding effects of drugs and their paired cues may contribute to relapse and persistent cocaine use. Glutaminergic actions in the ventral tegmental area (VTA) have been shown to regulate the rewarding effect of drugs and conditioned responses to drug-associated cues, but the role of the VTA in the acquisition, retrieval, and reconsolidation of cocaine cues is not yet known.
  
  
  METHODS
  In the present study, we used 7-chlorothiokynurenic acid (7-CTKA), an N-methyl-D-aspartate (NMDA) receptor glycine modulatory site antagonist with no rewarding effects, to examine the role of the NMDA receptor glycine modulatory site in the acquisition, retrieval, and reconsolidation of cocaine-related reward memory using the conditioned place preference (CPP) paradigm.
  
  
  RESULTS
  Separate groups of Sprague-Dawley rats were trained to acquire cocaine-induced CPP. Vehicle or 7-CTKA was microinjected into the VTA or substantia nigra (SN) (5 μg/μl) at different time points: 10 min before each CPP training session (acquisition), 10 min before the reactivation of CPP (retrieval), and immediately after the reactivation of CPP (reconsolidation). Cocaine-induced CPP was retested 24 h and 1 and 2 weeks after 7-CTKA administration. 7-CTKA microinjected into the VTA, but not SN, significantly impaired the acquisition, retrieval, and reconsolidation of cocaine-induced CPP without affecting cocaine-induced locomotion.
  
  
  CONCLUSIONS
  Our findings suggest that the NMDA receptor glycine modulatory site in the VTA plays a major role in cocaine reward memory, and NMDA receptor glycine site antagonists may be potential pharmacotherapies for the management of relapse.
authors: Insititute of Mental Health, Hebei Medical University, Shijiazhuang 050031, China.
authors: Shuang-jiang
authors: SJ
authors: Zhou
authors: Li-fen
authors: LF
authors: Xue
authors: Xue-yi
authors: XY
authors: Wang
authors: Wen-gao
authors: WG
authors: Jiang
authors: Yan-xue
authors: YX
authors: Xue
authors: Jian-feng
authors: JF
authors: Liu
authors: Yin-yin
authors: YY
authors: He
authors: Yi-xiao
authors: YX
authors: Luo
authors: Lin
authors: L
authors: Lu
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000502:physiology; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000502:physiology*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D003042:Cocaine; D005998:Glycine; D007736:Kynurenic Acid; D016194:Receptors, N-Methyl-D-Aspartate; C084485:7-chlorothiokynurenic acid