Chronic administration of morphine alters immediate-early gene expression in the forebrain of post-dependent rats

Abstract

Previous studies from this laboratory have demonstrated that acute, systemic administration of morphine results in an induction of the immediate-early gene (IEG) proteins, c-Fos and Jun-B, in the dorsomedial portion of the rat caudate–putamen (CPu). These studies have also shown that morphine can induce c-Fos in the central medial nucleus of the thalamus (CM). To determine whether this response is altered in post-dependent rats, twice-daily injections of an ascending dose of morphine were administered for 5 days, followed by a withdrawal period of 7 or 14 days. A challenge injection of morphine (10 mg/kg) was administered on the last day of withdrawal. As compared to an acute dose of morphine in a naive animal, the induction of c-Fos was increased in the dorsolateral CPu following challenge injection at 7 days, but not at 14 days. Induction of c-Fos in the CM following the challenge injection was blunted following 7 day, but not at 14 days, of withdrawal. An increase in the IEG protein, Jun-B, was also seen following 7 but not 14 days of withdrawal in both the dorsomedial and dorsolateral CPu. These findings demonstrate that a chronic treatment of morphine can result in altered patterns of IEG expression upon challenge with acute morphine, in a time-dependent manner, within the rat CPu and CM.