Morphine activation of c-fos expression in rat brain.

The post-receptor mechanism of opiate action has been studied by examining the activation by morphine of the proto-oncogene c-fos and its encoded nucleoprotein pp55c-fos (FOS) in rat caudate-putamen, which is rich in the mu-type opiate receptor. Following an acute morphine treatment, c-fos mRNA levels in rat caudate-putamen were increased to maximum (420% of control level) at 45 minutes and returned to control levels at 90 minutes. This induction was completely abolished by naloxone, a morphine antagonist. Fos protein, detected by immunocytochemistry, was also increased 3 hours after morphine injection, in the caudate-putamen, but not in the olfactory tubercle, which does not have the mu-type opiate receptor. Upon activation of opiate receptors by morphine, the c-fos gene is activated and Fos protein may act as a signal transducer uniquely involved in the mechanism of opiate addiction at the level of gene regulation.