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

用鸦片类药物（μ受体激动剂）和大麻素（CB1受体激动剂：WIN 55212-2）对新生大鼠离体脑干-脊髓制剂的吻侧腹外侧髓质（RVLM）吸气神经元的膜电位和阻力（Rm）进行测定。μ-阿片受体激动剂主要通过抑制髓质吸气神经元网络引起最终运动输出减少。这种对吸气神经元的抑制似乎是由于突触前和突触后的抑制。由吸气前神经元爆发率反映的中枢呼吸节律基本上未被激动剂改变。win55212 -2未引起呼吸抑制。使用CB1受体拮抗剂后，呼吸频率也未发生变化。μ-阿片受体激动剂使呼吸频率由8.4±1.9次/min降至2.7±1.8次/min。这种阿片类药物引起的呼吸抑制被WIN 55212-2从2.7±1.8次/min逆转到6.32±1.9次/min。

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.