The antinociceptive and sedative effects of carbachol and oxycodone administered into brainstem pontine reticular formation and spinal subarachnoid space in rats

To clarify the supraspinal and spinal actions of a cholinergic agonist, car bachol, and an opioid, oxycodone, we studied their antinociceptive and beha vioral effects when administered into brainstem medial pontine reticular fo rmation (mPRF) or spinal subarachnoid space with or without pretreatment of muscarinic receptor subtype antagonist. Sprague-Dawley rats were implanted with a 24-gauge stainless steel guide cannula into the mPRF and chronicall y implanted with a lumbar intrathecal catheter. Antinociception was tested using tail flick latency, motor coordination was evaluated by the rotarod t est, and overt sedation was assessed using a behavioral checklist. Carbacho l (0.5-4.0 mug) administered into the mPRF produced significant dose- and t ime-dependent antinociception, sedation, and motor dysfunction. These were completely blocked by pretreatment with atropine and the M-2 muscarinic ant agonist, methoctramine, and partially blocked by pretreatment with M-2 pire nzepine but not with M-3 p-fHHSiD. Oxycodone administered into the mPRF did not produce such effects. Spinal carbachol and oxycodone produced antinoci ception without any behavioral effects; their antinociceptive effects were completely blocked by pretreatment with atropine and M-2 antagonist. These results suggest that the antinociceptive action of carbachol is mediated by muscarinic cholinergic receptor activation, especially by M-2 receptor sub type in mPRF and spinal cord, and that although oxycodone seems unlikely to affect the cholinergic transmission of mPRF, spinal oxycodone-induced anal gesia is at least partly mediated via the activation of M-2 receptor subtyp e at the spinal cord.