Involvement of spinal adenosine A 1 and A 2 receptors in fentanyl-induced muscular rigidity in the rat

Abstract

In the present study, using hydrophilic adenosine antagonists either selective to A 1 or A 2 receptors, we investigated the central and spinal adenosinergic participation in fentanyl-induced muscular rigidity. Adult Sprague–Dawley rats were anesthetized with ketamine and were under mechanical ventilation. Fentanyl (100 μg/kg, i.v.) consistently elicited electromyographic (EMG) activation in the sacrococcygeal dorsalis lateralis muscle. This implied muscular rigidity was not blocked by i.c.v. administration of the adenosine A 1 antagonist, 1-allyl-3,7-dimethyl-8- p-sulfophenyl-xanthine (ADSPX; 20 or 40 nmol/2.5 μl), except at higher dose (80 nmol). Equimolar doses of the adenosine A 2 antagonist, 3,7-dimethyl-1-propargylxanthane (DMPX), did not exert any inhibitory effect on fentanyl-induced rigidity. Intrathecal (i.t.) administration of the same doses of ADSPX (20, 40 or 80 nmol/10 μl) appreciably suppressed the EMG activation. However, the rigidity was only inhibited by 40 or 80 nmol (i.t.) of DMPX, but not by the lowest dose. High-dose (80 nmol, i.t.) adenosine A 1 or A 2 antagonist per se did not induce motor impairment or hindlimb paralysis in conscious animals. These results suggest that adenosine A 1 and A 2 receptors in the spinal cord may play a more crucial role than those in the central nervous system (CNS) in fentanyl-induced muscular rigidity in rats.