title: Activity-regulated gene expression in immature neurons in the dentate gyrus following re-exposure to a cocaine-paired environment.
abstract: Intense craving for drug and relapse are observed in addicts who are exposed to environmental stimuli associated with drug-taking behavior even after long periods of abstinence. The hippocampus is a brain region known to be involved in contextual processing, taking place predominantly in the septal hippocampus, and emotional processing, taking place predominantly in the temporal hippocampus. Conditioned place preference is an animal model of context-conditioned reward. The dentate gyrus is a hippocampal sub-region particularly important for the acquisition of cocaine-induced place preference and is a site of continuous neurogenesis, which has been implicated in the vulnerability to drug-taking behavior. Therefore, these experiments explored the role of newly generated neurons in drug reward-context association by examining the activation, as determined by expression of the immediate early gene cfos, of young and mature granule cells in the septal and temporal dentate gyrus of adult rats that were re-exposed to a drug-paired environment following the development of cocaine place preference. The overall level of cfos expression was increased in both the septal and temporal dentate gyrus of animals that developed place preference and were re-exposed to the drug paired environment compared with re-exposure to a neutral environment. Overall level of neurogenesis, as detected by the S-phase marker 5'-bromo-2'-deoxyuridine (BrdU) and the immature neuron marker doublecortin (DCX), was unaltered by cocaine conditioning. However, the number of activated new neurons (DCX + cfos) was greater in the temporal dentate gyrus of cocaine-conditioned rats re-exposed to the drug-paired environment as compared to those re-exposed to a neutral environment. Further understanding of the role of dentate gyrus neurogenesis on the conditioned effects of drugs of abuse may provide new insights into the role of this process in the expression of addictive behaviors.
authors.affiliation: Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Barr
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008869:Microtubule-Associated Proteins; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: C000714848:Dcx protein, rat; D018765:Dopamine Uptake Inhibitors; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D001973:Bromodeoxyuridine; D003042:Cocaine
keywords: addiction; hippocampus; neurogenesis; reward; ventral