Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat.

Whereas muscular rigidity is a well-known side effect that is associated with high-dose fentanyl anesthesia, a paucity of information exists with regard to its underlying mechanism(s). We investigated in this study the possible engagement of locus coeruleus of the pons in this phenomenon, using male Sprague-Dawley rats anesthetized with ketamine. Under proper control of respiration, body temperature and end-tidal CO2, intravenous administration of fentanyl (50 or 100 micrograms/kg) consistently promoted an increase in electromyographic activity recorded from the gastrocnemius and abdominal rectus muscles. Such an induced muscular rigidity by the narcotic agent was significantly antagonized or even reduced by prior electrolytic lesions of the locus coeruleus or pretreatment with the alpha-adrenoceptor blocker, prazosin. Microinjection of fentanyl (2.5 micrograms/50 nl) directly into this pontine nucleus, on the other hand, elicited discernible electromyographic excitation. It is speculated that the induction of muscular rigidity by fentanyl may involve the coerulospinal noradrenergic fibers to the spinal motoneurons.