title: The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization.
abstract: Recently, the notion that memory and addiction share similar neural substrates has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the cornerstones of synaptic models of memory. The present study examined the effect of the competitive NMDAR antagonist CPP on the induction of behavioral sensitization and conditioned place preference to cocaine. Conditioned place preference is an associative memory model of drug seeking, while sensitization is a non-associative model of the transition from casual to compulsive use. There were three principal findings: (1) co-administration of CPP and cocaine altered the acute response to cocaine, suggesting a direct interaction between the two drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3) NMDAR antagonism abolished conditioned place preference. A review of prior evidence supporting a role for NMDARs in sensitization suggests that NMDAR antagonists directly interfere with cocaine's psychostimulant effects, and this interaction could be misinterpreted as a disruption of sensitization. Finally, we suggest that addiction recruits multiple kinds of plasticity, with sensitization recruiting NMDAR-independent mechanisms.
authors.affiliation: Molecular Cognition Laboratory, Department of Psychology, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0109,USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Carmack
authors.forename: Jeesun S
authors.initials: JS
authors.lastname: Kim
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Sage
authors.forename: Alaina W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Skillicorn
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Anagnostaras
mesh_terms: D000818:Animals; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D003042:Cocaine