Involvement of cerulospinal glutamatergic neurotransmission in fentanyl- induced muscular rigidity in the rat

Background: Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here. Methods: Electromyographic signals activated by bilateral microinjection of 2.5 μg fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg· kg^{- 1}· h^-1) was maintained until 10 min before fentanyl was administered. Results: Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square 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 administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5 methyl - 10,11 - 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)-propyl-1-phosphonic acid (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation. Conclusions: In addition to the cerulospinal noradrenergic mechanism, the cerulospinal glutamatergic pathway and both NMDA and non-NMDA receptors in the spinal cord may mediate fentanyl-induced muscular rigidity in the rat.