INVOLVEMENT OF G(0-ALPHA) SUBTYPE OF GUANINE-NUCLEOTIDE-BINDING REGULATORY PROTEIN AT THE LOCUS-COERULEUS IN FENTANYL-INDUCED MUSCULAR RIGIDITY IN THE RAT

Previous work from our laboratory suggested that locus coeruleus (LC) and the coerulospinal noradrenergic pathway are intimately related to the elicitation of muscular rigidity by fentanyl. The present study at tempted to identify the subtype of guanine nucleotide-binding regulato ry protein that may participate in this process, using Sprague-Dawley rats anesthetized with ketamine and under mechanical ventilation. Immu nofluorescent staining with a polyclonal antiserum directed against a 39-kDa protein that corresponds to the alpha subunit of G(o) revealed the presence of G(o alpha) immunoreactivity in neurons of the LC. Bila teral microinjection of the same G(o alpha) antiserum into the LC also significantly blunted the enhanced electromyographic activity recorde d from the sacrococcygeus dorsalis lateralis muscle induced by intrave nous administration of fentanyl (100 mu g/kg). These results suggest t hat G(o alpha) protein at the LC may participate in the signal transdu ction process that underlies muscular rigidity induced by high-dose fe ntanyl.