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 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 G alpha s and G alpha o mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, as alpha s mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, alpha a mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value of only after the fifth dose. The amounts of G alpha s and G alpha o 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.
Rubino
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Institute of Pharmacology, Faculty of Sciences, Milan, Italy.
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D000818:Animals; D001345:Autoradiography; D002490:Central Nervous System / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D009020:Morphine; D019204:GTP-Binding Proteins