title: Region and context-specific intracellular responses associated with cocaine-induced conditioned place preference expression.
abstract: The development and maintenance of cocaine addiction depend heavily on learned reward-environment associations that can induce drug-seeking behavior and relapse. Understanding the mechanisms underlying these cue-induced conditioned responses is important for relapse prevention. To test whether intracellular responses measured after cocaine conditioned place preference (CPP) expression are context-dependent, we re-exposed cocaine-treated rats (drug-free) to an environment previously paired with cocaine or saline, 24h after the CPP test. After 8 days of cocaine CPP training with one of two cocaine doses (5mg/kg or 20mg/kg, i.p.), CPP was expressed only after conditioning with the higher cocaine dose. In CPP expressing rats, locomotor responses after re-exposure to the cocaine-chamber were greater than in rats re-exposed to the saline-paired chamber. Nucleus Accumbens (NAc) phosphorylated ERK (pERK) levels were increased after re-exposure to the cocaine-paired, but not the saline-paired chamber, regardless of whether or not CPP behavior was expressed. Caudate Putamen (CPu) pERK and FosB protein levels increased after re-exposure to the cocaine chamber only after conditioning with the higher cocaine dose. Conversely, the higher cocaine dose, independent of environment, resulted in increased NAc FosB, ΔFosB and phosphorylated CREB (pCREB) protein levels compared to those conditioned with 5mg/kg cocaine (non-CPP-expressing). Our results suggest that NAc ERK phosphorylation may be involved with retrieving the contextual information of a cocaine-association, without necessarily motivating the expression of CPP behavior. Additionally, we show distinct patterns of intracellular responses in the NAc and CPu indicating a region-specific role for pERK/pCREB/FosB intracellular signaling in the retrieval of cocaine-context associations.
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA. Electronic address: stephanienygard@gmail.com.
authors.forename: S K
authors.initials: SK
authors.lastname: Nygard
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA. Electronic address: anthonyklambatsen@yahoo.com.
authors.forename: A
authors.initials: A
authors.lastname: Klambatsen
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA. Electronic address: bbalouch@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Balouch
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA. Electronic address: vaquinon@hunter.cuny.edu.
authors.forename: V
authors.initials: V
authors.lastname: Quinones-Jenab
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016, USA. Electronic address: sjenab@hunter.cuny.edu.
authors.forename: S
authors.initials: S
authors.lastname: Jenab
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine
keywords: CREB; ERK; FosB/ΔFosB; cocaine; conditioned place preference (CPP); striatum