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

Unilateral, site-specific microinjection of fentanyl (2.5 micrograms/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 alpha 1-adrenoceptor blocker, prazosin (250 micrograms/kg, i.v.). On the other hand, an equimolar dose (0.65 mumol/kg) of the specific alpha 2-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 alpha 1-adrenoceptors in the spinal cord.