INVOLVEMENT OF CERULOSPINAL GLUTAMATERGIC NEUROTRANSMISSION IN FENTANYL-INDUCED MUSCULAR RIGIDITY IN THE RAT

Background: Investigators in the author's laboratory previously establ ished the critical participation of the cerulospinal noradrenergic pat hway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ce ruleus neurons suggests a role for cerulospinal glutamatergic neurotra nsmission in fentanyl-induced muscular rigidity. This suggestion and t he subtype(s) of glutamate receptors involved were investigated here. Methods: Electromyographic signals activated by bilateral microinjecti on of 2.5 mu g fentanyl into the locus ceruleus were recorded differen tially from the left sacrococcygeus dorsi lateralis muscle of adult ma le Sprague-Dawley rats. The effect of intrathecal administration at th e lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular ri gidity was studied. Rats were under mechanical ventilation, and intrav enous infusion of ketamine (30 mg.kg(-1).h(-1)) was maintained until 1 0 min before fentanyl was administered. Results: Microinjection of fen tanyl bilaterally into the locus ceruleus increased the root mean squa re and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administratio n of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 0,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino- 5-phosphonovaleric acid (AP5), or -)-3-(2-carboxypiperazin-4-yl)-propy l-1-phosphonic acid (CPP). Intrathecal administration of kainic acid o r NMDA also resulted in significant electromyographic activation. Conc lusions: In addition to the cerulospinal noradrenergic mechanism, the cerulospinal glutamatergic pathway and both NMDA and non-NMDA receptor s in the spinal cord may mediate fentanyl-induced muscular rigidity in the rat.