title: Role of nucleus accumbens shell neuronal ensembles in context-induced reinstatement of cocaine-seeking.
abstract: Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B. On test day, reexposure to the cocaine-associated Context A reinstated cocaine seeking and increased expression of the neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core neurons. To assess a causal role for these activated neurons, we used the Daun02 inactivation procedure to selectively inactivate these neurons. We trained c-fos-lacZ transgenic rats to self-administer cocaine in Context A and extinguished their lever-pressing in Context B. On induction day, we exposed rats to either Context A or a novel Context C for 30 min and injected Daun02 or vehicle into accumbens shell or core 60 min later. On test day, 3 d after induction day, the ability of Context A to reinstate cocaine seeking and increase neuronal activity in accumbens shell was attenuated when Daun02 was previously injected after exposure to Context A. Daun02 injections after exposure to the novel Context C had no effect on context-induced reinstatement of cocaine seeking despite much greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections in accumbens core had no effect. Our data suggest that context-induced reinstatement of cocaine seeking is mediated by activation of context-selected accumbens shell but not core neuronal ensembles.
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Cruz
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Klil R
authors.initials: KR
authors.lastname: Babin
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Leao
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Evan M
authors.initials: EM
authors.lastname: Goldart
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bossert
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: Behavioral Neuroscience Branch, IRP/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224 bhope@intra.nida.nih.gov.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000473:pathology*; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012646:Self Administration
chemical_list: D003042:Cocaine
keywords: Daun02 inactivation; Fos; conditioned cues; drug environment; extinction; self-administration