Involvement of coerulospinal noradrenergic pathway in fentanyl-induced muscular rigidity in rats

Unilateral, site-specific microinjection of fentanyl ( 2.5 μg 50 nl) into the locus coeruleus (LC) in Sprague-Dawley rats anesthetized with ketamine evoked a significant increase in the electromyographic activity recorded from both caudal lateral extensor and gastrocnemius muscles. This correlate of opiate-induced muscular rigidity was appreciably antagonized by a pretreatment with the specific α₁-adrenoceptor blocker, prazosin (250 μg/kg, i.v.). On the other hand, an equimolar dose (0.65 μmol/kg) of the specific α₂-adrenoceptor blocker, yohimbine (0.23 mg/kg, i.v.) failed to prevent the occurrence of fentanyl-induced EMG activation. We suggest that the coerulospinal noradrenergic pathway may be directly involved in the elicitation of muscular rigidity by fentanyl, possibly via α₁-adrenoceptors in the spinal cord.