IMMEDIATE-EARLY GENE-EXPRESSION DURING MORPHINE-WITHDRAWAL

The expression of immediate early genes (IEG)s c-fos, c-jun and zif/268 was studied during naloxone-precipitated morphine withdrawal in various organs of the rat. Dependence was induced over a period of 6 days by a graded regimen of 6-hourly injections. Northern analysis revealed peak expression of all IEGs occurred in the forebrain plus cerebellum at 20 min and at 60 min in the brain stem following morphine withdrawal. Increased levels of c-fos and c-jun mRNA were observed in the spinal cord at 40 min of morphine withdrawal. An increase in c-fos and c-jun but not zif/268 mRNAs was seen in the jejunum between 20 and 60 min. Elevated levels of the IEG protein products in the cerebral cortex, hippocampus, thalamus, cerebellum, brain stem and spinal cord were observed at 60 min following morphine withdrawal. These data emphasize the temporal and spatial variation in IEG expression in different tissues during opiate withdrawal.