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

采用在体脑微透析法测定纹状体和伏隔核多巴胺释放，研究苯二氮类麻醉剂或镇静剂对中枢多巴胺能神经元活动的影响。研究了临床常用麻醉药可乐定和芬太尼对中枢多巴胺能神经元活动的影响。静脉注射咪达唑仑和氟硝西仑以剂量依赖的方式减少纹状体多巴胺的释放。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潘的影响。当注入纹状体时，氟硝基安定也减少纹状体多巴胺的释放，但当注入同侧黑质时，它并不影响多巴胺的释放。仅当药物同时注入两个部位时，中央给药咪达唑仑才有效。静脉注射咪达唑仑也呈剂量依赖性地减少伏隔核多巴胺的释放。相反，苯二氮卓类受体反向激动剂β-CCE剂量依赖性地增加多巴胺的释放。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受体介导的伏隔核多巴胺的减少。α_2肾上腺素能受体激动剂可乐定可减少伏隔核多巴胺的释放，增强咪达唑仑的作用。这一结果提示临床使用可乐定可减少咪达唑仑作为麻醉前药物时的麻醉需求。阿片类镇痛剂芬太尼以剂量依赖的方式增加伏隔核多巴胺的释放。这种作用可能是通过伏隔核机制来实现的。此外，咪达唑仑注入伏隔核可抑制芬太尼的作用，但不能阻断腹侧被盖区。

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.