INVOLVEMENT OF SPINAL ADENOSINE A(1) AND A(2) RECEPTORS IN FENTANYL-INDUCED MUSCULAR RIGIDITY IN THE RAT

In the present study, using hydrophilic adenosine antagonists either s elective to A(1) or A(2) receptors, we investigated the central and sp inal adenosinergic participation in fentanyl-induced muscular rigidity . Adult Sprague-Dawley rats were anesthetized with ketamine and were u nder mechanical ventilation. Fentanyl (100 mu g/kg, i.v.) consistently elicited electromyographic (EMG) activation in the sacrococcygeal dor salis 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 mu l), e xcept 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) adm inistration of the same doses of ADSPX (20, 40 or 80 nmol/10 mu l) app reciably 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 di d not induce motor impairment or hindlimb paralysis in conscious anima ls. These results suggest that adenosine A(1) and A(2) receptors in th e spinal cord may play a more crucial role than those in the central n ervous system (CNS) in fentanyl-induced muscular rigidity in rats. (C) 1997 Elsevier Science Ireland Ltd.