• Chunyu Jin, Hiroaki Araki, Mari Nagata, Riho Shimosaka, Kazuhiko Shibata, Katsuya Suemaru, Hiromu Kawasaki, and Yutaka Gomita.
• Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
• Behav. Brain Res. 2005 Jun 3;161(1):107-12.

AbstractConditioned 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.

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