Effects of general anaesthetics and sedatives on central dopaminergic neuronal activity : a microdialysis study

采用体内脑微透析法测定纹状体和伏隔核多巴胺释放量，研究苯二氮卓类麻醉药或镇静剂对中枢多巴胺能神经元活性的影响。本文还研究了临床常与麻醉药合用的药物，如氯定和芬太尼，对中枢多巴胺能神经元活性的影响。静脉注射咪达唑仑和氟硝西泮以剂量依赖的方式减少纹状体多巴胺释放。氟马西尼也不影响纹状体多巴胺的释放，但它阻止了咪达唑仑和氟硝西泮的作用。氟硝西泮注入纹状体后也能降低纹状体多巴胺的释放，但注入同侧黑质后对纹状体多巴胺的释放没有影响。只有当药物同时注入两个部位时，咪达唑仑的中央管理才有效。静脉注射咪达唑仑也会剂量依赖性地减少伏隔核释放的多巴胺。相反，苯二氮卓受体逆激动剂β - cce剂量依赖性地增加了多巴胺的释放。氟马西尼再次阻止了这两种药物的作用。此外，腺苷受体不参与苯二氮卓类受体介导的伏隔核多巴胺减少。可乐定是一种alpha_2-肾上腺素能受体激动剂，可减少伏隔核释放多巴胺，增强咪达唑仑的作用。结果提示，临床使用可乐定，以减少咪达唑仑的麻醉需求时，作为一种预用药。芬太尼，一种阿片类镇痛药，增加多巴胺释放伏隔核在一个依赖的方式。这种影响可能是由伏隔核机制介导的。此外，注入伏隔核的咪达唑仑可抑制芬太尼的作用，但未注入腹侧被盖区。

Effects of benzodiazepine anaesthetics or sedatives on central dopaminergic neuronal activity were studied by using in vivo brain microdialysis to measure dopamine release from the striatum and the nucleus accumbens. Effects of the drugs often coadministered in clinic with the anaesthetics, i.e.clonidine and fentanyl, on central dopaminergic neuronal activity were also studied. Intravenous injections of midazolam and flunitrazepam decreased striatal dopamine release in a dose-dependent manner. Flumazenil also did not affect striatal dopamine release, but it prevented the effects of midazolam and flunitrazepam. Flunitrazepam also decreased striatal dopamine release when infused into the striatum, but it failed to affect the dopamine release when infused into the ipsilateral substantia nigra. Central administrations of midazolam were effective only when the drug was infused into both sites simultaneously. Intravenous injections of midazolam also dose-dependently decreased dopamine release from the nucleus accumbens. In contrast, the benzodiazepine receptor inverse agonist, beta-CCE,dosedependently increased the dopamini release. The effects of both drugs were prevented again by flumazenil. Moreover, adenosine receptors were not suggested to be involved in the benzodiazepine receptor-mediated dopamine decrease from the nucleus accumbens. Clonidine, an alpha_2-adrenoceptor agonist, decreased dopamine release from the nucleus accumbens, and enhanced the effects of midazolam. The results are suggestive of clinical use of clonidine to reduce the anaesthtic requirement of midazolam when used as a premedicant. Fentanyl, an opioid analgesic, increased dopamine release from the nucleus accumbens in a does-dependent manner. The effects were suggested to be mediated by the nucleus accumbens mechanisms. Furthermore, the effects of fentanyl was inhibited by midazolam infused into the nucleus accumbens but not infused into the ventral tegmental area.