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

Rationale 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...

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Bibliographic Details
Published in:Psychopharmacologia 2012-02, Vol.219 (3), p.751-761
Main Authors: 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.
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Alcohol
Alcohol, Denatured
Animals
Autoshaping
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Conditioned reinforcement
Conditioning, Operant - drug effects
Dizocilpine Maleate - pharmacology
Drug abuse
Drug addiction
Ethanol
Ethanol - administration & dosage
Excitatory Amino Acid Antagonists - pharmacology
Glutamic acid receptors
Glutamic acid receptors (ionotropic)
Male
Medical sciences
Memory
Mental disorders
Methyl aspartate
MK-801
Motivation
N-Methyl-D-aspartic acid receptors
Nervous system diseases
Neurosciences
Neurotransmission
Original Investigation
Pharmacology/Toxicology
Propranolol
Propranolol hydrochloride
Psychiatry
Rats
Receptor mechanisms
Receptors, Adrenergic, beta - physiology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - physiology
Reinforcement
Self Administration
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Summary:Rationale 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 β-adrenergic receptor (βAR)-mediated signalling. However, it is unknown whether the drug cue memory representations underlying conditioned approach and PIT depend upon the same mechanisms. Objectives 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 βAR- and NMDAR-dependent neurotransmission. Results 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 βAR antagonist propranolol, when given in conjunction with memory reactivation. Conclusions As for natural reinforcers, NMDARs are required for the reconsolidation of all aspects of pavlovian drug memories, but βARs 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.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-011-2399-9