title: Expression of c-Fos in the rat central amygdala accompanies the acquisition but not expression of conditioned place aversion induced by withdrawal from acute morphine dependence.
abstract: Conditioned reinforcement is hypothesized to be critically involved in drug addiction as a factor contributing to compulsive drug use and relapse. The present study focused on the neurobiology involved in the acquisition and expression of conditioned reinforcing effects of morphine withdrawal employing a conditioned place aversion (CPA) paradigm in acute-dependent rats. Expression of c-Fos in the amygdala (the central nucleus, CeA; the medial nucleus, MeA; the basolateral nucleus, BLA) following naloxone-precipitated withdrawal and the CPA test was examined using a range of naloxone doses (0.02, 0.05, 0.1, 0.2, 0.5 and 1.0 mg/kg). Naloxone dose-dependently produced CPA in rats given a single morphine exposure. In CeA, but not MeA with high-level constitutive neuronal activity, the naloxone-induced modification in c-Fos immunoreactivity following morphine pretreatment exhibited a dose-dependent pattern similar to that seen in the behavioral study. On the other hand, none of the three amygdaloid nuclei examined including CeA, MeA and BLA showed notable sensitivity of c-Fos to the conditioned withdrawal stimulus. These results suggest that CeA may play a role in the negative affective aspect of withdrawal from acute dependence, and in part suggest that the acquisition and expression of CPA may involve different neurobiological mechanisms.
authors.affiliation: Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Jin
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Araki
authors.forename: Mari
authors.initials: M
authors.lastname: Nagata
authors.forename: Riho
authors.initials: R
authors.lastname: Shimosaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shibata
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suemaru
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Gomita
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000378:metabolism* / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D009020:Morphine