Inhibition by intrathecal prazosin but not yohimbine of fentanyl-induced muscular rigidity in the rat

We evaluated the effect of intrathecally administered prazosin, α₁-adrenoceptor antagonist, or yohimbine, α₂-adrenoceptor antagonist, on fentanyl-induced muscular rigidity. Adult, male Sprague-Dawley rats were anesthetized with ketamine and were under mechanical ventilation. Fentanyl given intravenously (100 μg/kg) or microinjected into the bilateral locus coeruleus (LC) (2.5 μg/50 nl) consistently evoked a significant increase in the electromyographic activity recorded from the sacrococcygeus dorsalis lateralis muscle. This implied muscular rigidity was appreciably antagonized by prior intrathecal (10 μl) administration of prazosin (5 or 10 nmol), but not equimolar dose of yohimbine. These results suggest that the spinal α₁-adrenoceptors in the coerulospinal noradrenergic pathway play a key role in fentanyl-induced muscular rigidity.