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

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.