DISTRIBUTION OF C-FOS IN GUINEA-PIG BRAIN FOLLOWING MORPHINE-WITHDRAWAL

The distribution of the immediate-early gene and transcription factor protein, c-Fos, was examined in the brains of guinea-pigs following tr eatment with morphine: naloxone or naltrexone, or the induction of mor phine withdrawal by these opioid antagonists. Guinea-pigs were given s ubcutaneous injections of morphine sulphate or tartrate three times pe r day in increasing doses for three days (total dose 690 mg/kg as base ). Control animals received saline injections. Naloxone hydrochloride (30 mg/kg), naltrexone hydrochloride (15 mg/kg) or saline was administ ered subcutaneously 1 h after the last dose of morphine or saline, and the animals killed 1.5 h later by perfusion-fixation under deep sodiu m pentobarbitone anaesthesia. In the animals that were treated with mo rphine and withdrawn with either naloxone or naltrexone, c-Fos was exp ressed in neurons in many brain areas, including the frontal and cingu late cortices, olfactory tubercles, ventral pallidum, nucleus accumben s, habenular, paraventricular thalamic nucleus, septal and arcuate nuc lei, lateral and posterior hypothalamic areas, ventral tegmental area, central grey, dorsal raphe nucleus, locus coeruleus, raphe magnus, la teral paragigantocellular nucleus and solitary tract nucleus. In contr ast, only low levels of c-Fos were found in brains of animals that had been treated for three days with morphine followed by saline, or with saline followed by naltrexone or naloxone. The widespread distributio n of c-Fos induced by morphine withdrawal reflects the complexity of t he accompanying behavioural and autonomic responses.