Differential effects of prazosin and yohimbine on fentanyl-induced muscular rigidity in rats

Abstract Whereas muscular rigidity is a well-known phenomenon that is related to anesthesia induced by large doses of narcotic drugs, the precise underlying mechanism(s) remain to be fully elucidated. This study investigated the possible role of noradrenergic neurotransmission and the participation of α-adrenoceptors in this phenomenon. Male Sprague-Dawley rats, under ketamine-induced anesthesia (120 mg/kg, i.p.) and with proper control of respiration, body temperature and end-tidal CO 2 were used. Intravenous administration of fentanyl (lOO g/kg) consistently caused a significant increase in the electromyographic (EMG) activity, recorded from both gastrocnemius and abdominal reetus muscles. This implied muscular rigidity was markedly antagonized by pretreatment with the specific α 1 -adrenoceptor blocker, prazosin (50 or 250μg/kg, i.V.). This antagonism occurred in spite of a high level of fentanyl in the plasma, as determined by radioimmunoassay. The specific α 2 -adrenoceptor blocker, yohimbine (1.15 or 2.3 mg/kg, i.V.), on the other hand, not only failed to prevent fentanyl-induced activation of the EMG, but actually potentiated the response. It is concluded that noradrenergic neurotransmission, possibly originating from the locus coeruleus, may participate in the elicitation of muscular rigidity by fentanyl. Furthermore, this process may involve an excitatory action through α 1 -, and an inhibitory action through α 2 -adrenoceptors, in the spinal cord.