Attenuation of the fentanyl-induced muscle rigidity by the selective 5HT1A agonist 8-OH-DPAT

Fentanyl given in a low dose of 25 microgram/kg (ip) evoked a marked muscle rigidity measured directly by a mechanographic method in non-anesthetized rats. The selective 5HT1A receptor agonist 8-OH-DPAT (0.1, 0.3 and 1.0 mg/kg ip) showed only a tendency to attenuate the natural muscle tone. However, when that compound was given 40 min before (0.3 and 1.0 mg/kg ip) or 20 min after (1.0 mg/kg ip) fentanyl, it abolished the muscle rigidity. It is concluded that the serotonergic transmission, possibly via 5HT1A receptors, may participate in elucidation of the mechanism(s) of the fentanyl-induced muscle rigidity. These results seem to be clinically important in case other 5HT1A agonists, buspirone or gepirone (potent anxiolytics), also prevented fentanyl-induced muscle rigidity in humans.