Antagonism at NMDA receptors, but not beta-adrenergic receptors, disrupts the reconsolidation of pavlovian conditioned approach and instrumental transfer for ethanol-associated conditioned stimuli

作者：Milton Amy L^*; Schramm Moritz J W; Wawrzynski James R; Gore Felicity; Oikonomou Mpegeti Faye; Wang Nancy Q; Samuel Daniel; Economidou Daina; Everitt Barry J

来源：Psychopharmacology, 2012, 219(3): 751-761.

DOI：10.1007/s00213-011-2399-9

• Memory reconsolidation
• NMDA receptor
• beta-adrenergic receptor
• Pavlovian conditioned approach
• Pavlovian-instrumental transfer
• Alcohol

Reconsolidation is the process by which memories require restabilisation following destabilisation at retrieval. Since even old, well-established memories become susceptible to disruption following reactivation, treatments based upon disrupting reconsolidation could provide a novel form of therapy for neuropsychiatric disorders based upon maladaptive memories, such as drug addiction. Pavlovian cues are potent precipitators of relapse to drug-seeking behaviour and influence instrumental drug seeking through at least three psychologically and neurobiologically distinct processes: conditioned reinforcement, conditioned approach (autoshaping) and conditioned motivation (pavlovian-instrumental transfer or PIT). We have previously demonstrated that the reconsolidation of memories underlying the conditioned reinforcing properties of drug cues depends upon NMDA receptor (NMDAR)- and beta-adrenergic receptor (beta AR)-mediated signalling. However, it is unknown whether the drug cue memory representations underlying conditioned approach and PIT depend upon the same mechanisms.
Using orally self-administered ethanol as a reinforcer in two separate experiments, we investigated whether the reconsolidation of the memories underlying conditioned approach and PIT requires beta AR- and NMDAR-dependent neurotransmission.
For ethanol self-administering but non-dependent rats, the memories underlying conditioned approach and PIT for a pavlovian drug cue were disrupted by the administration of the NMDAR antagonist MK-801, but not the administration of the beta AR antagonist propranolol, when given in conjunction with memory reactivation.
As for natural reinforcers, NMDARs are required for the reconsolidation of all aspects of pavlovian drug memories, but beta ARs are only required for the memory representation underlying conditioned reinforcement. These results indicate the potential utility of treatments based upon disrupting cue-drug memory reconsolidation in preventing relapse.

• 出版日期2012-2