EFFECT OF CHRONIC EXPOSURE TO NALTREXONE AND OPIOID SELECTIVE AGONISTS ON G-PROTEIN MESSENGER-RNA LEVELS IN THE RAT NERVOUS-SYSTEM

The in situ hybridization technique was used to investigate the effect on G protein alpha subunit expression throughout the brain of rats ch ronically infused with naltrexone (70 mu g/mu l, 1 mu l/h), DAGO (0.5 mu g/mu l, 1 mu l/h), DADLE (11.4 mu g/mu l, 1 mu l/h), DPDPE (3.4 mu g/mu l, 1 mu l/h) and U-50,488H (4 mu g/mu l, 1 mu l/h). Prolonged exp osure to naltrexone did not modify G protein alpha subunit mRNA expres sion, whereas DADLE and U-50,488H, respectively, increased the levels of alpha s and alpha o mRNA in specific brain regions. In particular, a 15% increase in alpha s expression was only observed in the dorsomed ial hypothalamic nucleus of rats undergoing chronic DADLE infusion: a 15% increase in alpha o levels was detected in the claustrum and endop iriform nucleus of rats chronically treated with U-50,488H. These are the first in vivo data to demonstrate that only chronic stimulation wi th an opioid agonist (morphine and/or DADLE and U-50,488H) is capable of modifying G protein alpha subunit mRNA. The regional selectivity of these modifications is discussed, together with the receptor specific ity of the opioid effects.