期刊
NEUROBIOLOGY OF LEARNING AND MEMORY
卷 88, 期 4, 页码 435-444出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2007.05.006
关键词
amygdala; NMDA; glutamate; cocaine; relapse; reinstatement
资金
- NCRR NIH HHS [C06 RR015455] Funding Source: Medline
- NIDA NIH HHS [R01 DA010462-09, R01 DA010462-10, R01 DA010462, DA010462, T32 DA007288, DA07288] Funding Source: Medline
Previous research from our laboratory has implicated the basolateral amygdala (BLA) complex in the acquisition and consolidation of cue-cocaine associations, as well as extinction learning, which may regulate the long-lasting control of conditioned stimuli (CS) over drug-seeking behavior. Given the well established role of NMDA glutamate receptor activation in other forms of amygdalar-based learning, we predicted that BLA-mediated drug-cue associative learning would be NMDA receptor dependent. To test this hypothesis, male Sprague-Dawley rats self-administered i.v. cocaine (0.6 mg/kg/infusion) in the absence of explicit CS pairings (2-h sessions, 5 days), followed by a single I-h classical conditioning (CC) session, during which they received passive infusions of cocaine discretely paired with a light + tone stimulus complex. Following additional cocaine self-administration sessions in the absence of the CS (2-h sessions, 5 days) and extinction training sessions (no cocaine or CS presentation, 2-h sessions, 7 days), the ability of the CS to reinstate cocaine-seeking on three test days was assessed. Rats received bilateral intra-BLA infusions (0.5 mu l/hemisphere) of vehicle or the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP-5), immediately prior to the CC session (acquisition), immediately following the CC session (consolidation), or immediately following reinstatement testing (consolidation of conditioned-cued extinction learning). AP-5 administered before or after CC attenuated subsequent CS-induced reinstatement, whereas AP-5 administered immediately following the first two reinstatement tests impaired the extinction of cocaine-seeking behavior. These results suggest that NMDA receptor-mediated mechanisms within the BLA play a crucial role in the consolidation of drug-CS associations into long-term memories that, in turn, drive cocaine-seeking during relapse. (C) 2007 Elsevier Inc. All rights reserved.
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