Evaluation of opioid and cannabinoid-induce respiratory center inhibition in medulla

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Membrane potential and resistance (Rm) were measured in inspiratory neurons in rostral ventrolateral medulla (RVLM) of the isolated brainstem-spinal cord preparation from newborn rats during bath application of opioids (μ-receptor agonists) and cannabinoid (CB1 receptor agonist : WIN 55212-2). μ-opioid receptor agonist caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be due to both a pre-and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists. WIN 55212-2 did not induced respiratory depression. Respiratory rate did not also change after application of CB1 receptor antagonist. Respiratory rate was decreased after application of μ-opioid receptor agonist from 8.4±1.9 to 2.7±1.8 bursts/min. This opioid-induced respiratory depression was parcially reversed by WIN 55212-2 from 2.7±1.8 to 6.32±1.9 bursts/min.