Medial prefrontal cortex infusions of bupivacaine or AP-5 block extinction of amphetamine conditioned place preference.
The present experiments used reversible lesion techniques and intra-mPFC infusions of the n-methyl D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP-5) to examine the role of the mPFC in extinction of an amphetamine conditioned place preference (CPP). Following initial training and testing for an amphetamine (2 mg/kg) CPP, adult male Long-Evans rats were given extinction trials that were identical to training, except in the absence of peripheral amphetamine injections. Immediately prior to each extinction trial, rats received intra-mPFC infusions of the anesthetic drug bupivacaine (0.75% solution/0.5 microl), AP-5 (1.25, 2.5, 5.0 microg/0.5 microl), or saline. Following extinction training, rats were given a second CPP test session. Rats receiving intra-mPFC infusions of saline displayed extinction of CPP behavior. In contrast, intra-mPFC infusions of bupivacaine or AP-5 (2.5, 5.0 microg) blocked CPP extinction. The findings indicate (1) the mPFC mediates extinction of approach behavior to drug-associated environmental contexts, and (2) NMDA receptor blockade within the mPFC is sufficient to block extinction of amphetamine CPP behavior.
Hsu
Emily
E
Department of Psychology, Yale University, New Haven, CT 06520, USA.
Packard
Mark G
MG
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002045:Bupivacaine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000779:Anesthetics, Local; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; D000661:Amphetamine; D002045:Bupivacaine