MORPHINE-WITHDRAWAL SYNDROME AND G-PROTEIN EXPRESSION - A STUDY OF THE TIME-COURSE IN THE RAT CENTRAL-NERVOUS-SYSTEM

We followed the changes in G protein alpha subunit expression and leve ls throughout the brain during the naltrexone-precipitated withdrawal syndrome in morphine-dependent rats. Intraperitoneally injected naltre xone (10 mg/kg) in rats made tolerant to morphine resulted in sustaine d withdrawal, Additional naltrexone doses 6, 24 and 72 h later still i nduced a significant abstinence syndrome. At the fifth naltrexone inje ction (8 days later) counted signs were completely resolved but checke d ones were not. Besides the behavioural modifications, opiate withdra wal affected G protein expression in the central nervous system. In si tu hybridization showed that G alpha s and G alpha o mRNA, whose level s are increased in tolerance, changed further during opiate withdrawal . Specifically, the as mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subseque nt doses. However, alpha o mRNA expression in the olfactory system rem ained elevated after repeated naltrexone injections, declining to the control value only after the fifth dose. The amounts of G alpha s and G alpha o protein closely followed the time course of mRNA. The relati onship between behavioural and biochemical parameters is discussed, to gether with the regional selectivity of the modifications.