Involvement of spinal adenosine A1 and A2 receptors in fentanyl-induced muscular rigidity in the rat.
In the present study, using hydrophilic adenosine antagonists either selective to A1 or A2 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 micrograms/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 A1 antagonist, 1-allyl-3,7-dimethyl-8-p-sulfophenyl-xanthine (ADSPX; 20 or 40 nmol/2.5 microliters), except at higher dose (80 nmol). Equimolar doses of the adenosine A2 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 microliters) 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 A1 or A2 antagonist per se did not induce motor impairment or hindlimb paralysis in conscious animals. These results suggest that adenosine A1 and A2 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.
Lui
P W
PW
Department of Anesthesiology, Veterans General Hospital-Taipei 201, Taiwan, ROC. pwlui@vghtpe.gov.tw
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D018047:Receptors, Purinergic P1; D005283:Fentanyl