Differential effect of NMDA receptor antagonist in the nucleus accumbens on reconsolidation of morphine -related positive and aversive memory in rats

Dysfunctional reconsolidation processes may help drug memories resist extinction and contribute to high rate of relapse. Reconsolidation of drug memory is mainly affected by the appetitive and aversive emotional experiences associated with an addictive drug. The nucleus accumbens has been shown to mediate the reconsolidation of positive emotional addictive memory, but its role in negative emotional addictive memory remains elusive. In the present study, we used morphine-induced CPP (m-CPP) and morphine-naloxone induced conditioned place aversion (m-CPA) to investigate the role of N-methyl-D-aspartate (NMDA) receptors within the nucleus accumbens on reconsolidation of emotional drug memory. Here we demonstrate that infusion of the NMDA receptor antagonist, D-(-)-2 amino-5-phosphonopentanoic acid ((D)-APV). into the nucleus accumbens before memory reactivation disrupts the reconsolidation of m-CPP, but does not affect m-CPA. The effect on m-CPP reconsolidation depended on memory reactivation: (D)-APV infusion had no effect in the absence of reactivation. The findings show that the glutamatergic NMDA receptor in nucleus accumbens mechanisms involved in reconsolidating aversive and positive morphine-associated memories can be dissociated. (C) 2011 Elsevier B.V. All rights reserved

Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral caudate-putamen in cue-induced morphine seeking after prolonged abstinence and the underlying D1- and D2-like receptor mechanisms in rats

Drug-associated cues can elicit relapse to drug seeking after abstinence. Studies with extinction-reinstatement models implicate dopamine (DA) in the nucleus accumbens shell (NAshell) and dorsolateral caudate-putamen (dlCPu) in cocaine seeking. However, less is known about their roles in cue-induced opiate seeking after prolonged abstinence. Using a morphine self-administration and abstinence-relapse model, we explored the roles of NAshell and dlCPu DA and the D1/D2-like receptor mechanisms underlying morphine rewarding and/or seeking. Acquisition of morphine self-administration was examined following 6-Hydroxydopamine hydrobromide (6-OHDA) lesions of the NAshell and dlCPu. For morphine seeking, rats underwent 3 weeks' morphine self-administration followed by 3 weeks' abstinence from morphine and the training environment. Prior to testing, 6-OHDA, D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected; then rats were exposed to morphine-associated contextual and discrete cues. Results show that acquisition of morphine self-administration was inhibited by NAshell (not dlCPu) lesions, while morphine seeking was attenuated by lesions of either region, by D1 (not D2) receptor blockade in NAshell, or by blockade of either D1 or D2 receptors in dlCPu. These data indicate a critical role of dopaminergic transmission in the NAshell (via D1-like receptors) and dlCPu (via D1- and D2-like receptors) in morphine seeking after prolonged abstinence