Cannabinoidergic and opioidergic inhibition of spinal reflexes in the decerebrated, spinalized rabbit

The present experiments were designed to investigate the role(s) of cannabinoid receptors in modulating transmission in the sural-medial gastrocnemius withdrawal reflex of the decerebrated, spinalized rabbit and how, if present, cannabinoid-mediated control might interact with opioid-mediated inhibitions known to impinge on this reflex pathway. The selective CB1 receptor antagonist SR 141716A enhanced reflexes by a factor of two after a cumulative dose of 100 nmol kg(-1) i.v., but had no effect on the endogenous opioid-mediated inhibition generated by repetitive electrical stimulation of the common peroneal nerve, or on the suppression of reflexes caused by i.v. administration of the synthetic opioid fentanyl. Given at a dose of 10 nmol kg(-1) i.v., the potent, CB1-CB2 cannabinoid receptor agonist HU 210 inhibited medial gastrocnemius reflexes to approximately 30% of controls and significantly decreased both heart rate and blood pressure, but did not alter the inhibition of reflexes resulting from common peroneal nerve stimulation or i.v. fentanyl. The effects of HU 210 were reversed by SR 141716A. HU 210 was just as effective in inhibiting reflexes in the presence of the opioid antagonist naloxone (5 mu mol kg(-1)) as it was in untreated animals. The data show that cannabinoids, acting through CB1 receptors, are inhibitory in rabbit spinal cord and that there appears to be some endogenous cannabinoid tone under the conditions of the present experiments. The evidence of this study is that the inhibitory effects Of opioids and cannabinoids in rabbit spinal cord are completely independent of each other, and rue additive rather than synergistic. (C) 2001 Elsevier Science Ltd. All rights reserved.