title: Variations in the stimulus salience of cocaine reward influences drug-associated contextual memory.
abstract: Drugs of abuse act as reinforcers because they influence learning and memory processes resulting in long-term memory of drug reward. We have previously shown that mice conditioned by fixed daily dose of cocaine (Fix-C) or daily escalating doses of cocaine (Esc-C) resulted in short- and long-term persistence of drug memory, respectively, suggesting different mechanisms in acquisition of cocaine memory. The present study was undertaken to investigate the differential contribution of N-methyl-D-aspartate receptor (NMDAR) subunits in the formation of Fix-C and Esc-C memory in C57BL/6J mice. Training by Esc-C resulted in marked elevation in hippocampal expression of Grin2b mRNA and NR2B protein levels compared with training by Fix-C. The NR2B-containing NMDAR antagonist ifenprodil had similar attenuating effects on acquisition and reconsolidation of Fix-C and Esc-C memory. However, the NMDAR antagonist MK-801 had differential effects: (1) higher doses of MK-801 were required for post-retrieval disruption of reconsolidation of Esc-C memory than Fix-C memory; and (2) pre-retrieval MK-801 inhibited extinction of Fix-C memory but it had no effect on Esc-C memory. In addition, blockade of NMDAR downstream signaling pathways also showed differential regulation of Fix-C and Esc-C memory. Inhibition of neuronal nitric oxide synthase attenuated acquisition and disrupted reconsolidation of Fix-C but not Esc-C memory. In contrast, the mitogen-activating extracellular kinase inhibitor SL327 attenuated reconsolidation of Esc-C but not Fix-C memory. These results suggest that NMDAR downstream signaling molecules associated with consolidation and reconsolidation of cocaine-associated memory may vary upon changes in the salience of cocaine reward during conditioning.
authors.affiliation: Division of Neuroscience, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Shervin
authors.initials: S
authors.lastname: Liddie
authors.affiliation: Division of Neuroscience, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Yossef
authors.initials: Y
authors.lastname: Itzhak
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C424127:SL 327; D000607:Aminoacetonitrile; D016291:Dizocilpine Maleate; C095106:traxoprodil mesylate; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D003042:Cocaine; C010739:ifenprodil
keywords: Addiction; NR2B; cocaine; place preference; reconsolidation