The effects of extinction training in reducing the reinstatement of drug-seeking behavior: Involvement of NMDA receptors

Although the process of extinction has been well documented for various forms of behavioral responses, the effects of extinction on the reinstatement of drug-seeking behavior are relatively understudied. In this report, the effectiveness of an extinction training protocol to reduce primed reinstatement responses was compared with the effectiveness of an equivalent period of enforced abstinence. We found that extinction training performed in the drug taking environment significantly reduced reinstatement behavior subsequently primed by either contextual cues, conditioned cues, or cocaine infusion. The ability of extinction to reduce cocaine primed reinstatement was blocked by the systemic administration of the competitive NMDAR antagonist ((+/-)CPP, 5 mg/kg i.p.) administered prior to each extinction training session. Interestingly, this pharmacological intervention had no impact on the effectiveness of extinction to reduce drug-seeking behavior primed by either contextual cues or conditioned cues. These results suggest that an extinction training experience involves multiple mechanisms that can be dissociated into nonNMDAR and NMDAR dependent components with respect to the type of reinstatement (i.e. context-, conditioned stimuli (CS)-, or drug-induced) being assessed. (C) 2007 Elsevier B.V. All rights reserved.