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

Previous studies from this laboratory have demonstrated that acute, systemi c administration of morphine results in an induction of the: immediate-earl y gene (IEG) proteins, c-Fos and Jun-B, in the dorsomedial portion of the r at caudate-putamen (CPu). These studies have also shown that morphine can i nduce c-Fos in the central medial nucleus of the thalamus (CM). To determin e whether this response is altered in post-dependent rats, twice-daily inje ctions of an ascending dose of morphine were administered fur 5 days, follo wed by a withdrawal period of 7 or 14 days. A challenge injection of morphi ne (10 mg/kg) was administered on the last day of withdrawal. As compared t o an acute dose of morphine in a naive animal, the induction of c-Fos was i ncreased in the dorsolateral CPu following challenge injection at 7 days, b ut not at 14 days. induction of c-Fos in the CM following the challenge inj ection was blunted following 7 day, but not at 14 days, of withdrawal. An i ncrease in the IEG protein, Jun-B, was also seen following 7 but not 14 day s of withdrawal in both the dorsomedial and dorsolateral CPu. These finding s demonstrate that a chronic treatment of morphine can result in altered pa tterns of IEG expression upon challenge with acute morphine, in a time-depe ndent manner, within the rat CPu and CM. (C) 1999 Elsevier Science B.V. All rights reserved.