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 α subunit expression and levels throughout the brain during the naltrexone‐precipitated withdrawal syndrome in morphine‐dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At the fifth naltrexone injection (8 days later) counted signs were completely resolved but checked ones were not. Besides the behavioural modifications, opiate withdrawal affected G protein expression in the central nervous system. In situ hybridization showed that Gαs and Gαo mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, the αs mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, αo mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value only after the fifth dose. The amounts of Gαs and Gαo protein closely followed the time course of mRNA. The relationship between behavioural and biochemical parameters is discussed, together with the regional selectivity of the modifications. Copyright © 1995, Wiley Blackwell. All rights reserved