Investigation of the descending noradrenergic Inhibitory pathway using nitrous oxide as a probe

最近的研究表明，一氧化二氮可以激活脑干中的去甲肾上腺素能神经元和脊髓中的GABA能神经元。然而，介导这些事件的确切神经通路仍有待确定。在成年雄性Fischer大鼠中，脑室内应用抗DSSH-Saporin选择性地损害了去甲肾上腺素能核团。然后给予一氧化二氮染毒，观察大鼠脊髓内GABA能神经元的c-Fos免疫反应。与未破坏去甲肾上腺素能核的对照组大鼠相比，抗DSSH-Saporin处理组大鼠FOS免疫反应减弱。在接下来的研究中，成年雄性Fischer大鼠脑室注射α-Helical CRH(促肾上腺皮质激素释放因子受体拮抗剂)、DAMGO(阿片受体激动剂)和Naloxne(阿片受体拮抗剂)。然后给予一氧化二氮暴露，检测脑干去甲肾上腺素能核(蓝斑)c-Fos免疫反应。α螺旋促肾上腺皮质激素释放激素和纳洛酮治疗后c-Fos免疫反应减弱，提示促肾上腺皮质激素释放因子和阿片类药物共同参与脑干去甲肾上腺素能神经元的激活。

Recent studies have revealed that nitrous oxide activates noradrenergic neurons in the brain stem and GABAergic neurons in the spinal cord. However, the precise neuronal pathways that mediate these events remain to be determined.In adult male Fischer rats, noradrenergic nuclei of the brain stem were selectively lesioned by intracerebroventricular application of anti-DssH-saporin. After that rats were exposed to nitrous oxide, and c-Fos immunostaining of GABAergic neurons was examined in the spinal cord. Fos immunoreactivity was diminished in the anti-DssH-saporin treated rats than control rats which were not destroyed noradrenergic nuclei. This result shows that noradrenergic nuclei of the brain stem are essential for nitrous oxide to activate GABAergic neurons in the spinal cord.In the following study, adult male Fischer rats were administered α-helical CRH (a corticotropin releasing factor receptor antagonist), DAMGO (an opioid receptor agonist), and naloxne (an opioid receptor antagonist) intracerebroventricularly. Then they were exposed to nitrous oxide, and c-Fos immunoreactivity of brain stem noradrenergic nucleus (locus coeruleus) was examined. Diminishing of c-Fos immunoreactivity inα-helical CRH and naloxone administered rats suggests that both corticotropin releasing factor and opioid are involved in the activation of noradrenergic neurons in the brain stem.