Irifune M, Sato T, Nishikawa T, Masuyama T, Nomoto M, Fukuda T, Kawahara M
Department of Pharmacology, Kagoshima University Dental School, Japan.
Anesthesiology. 1997 Feb;86(2):464-75. doi: 10.1097/00000542-199702000-00022.
It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice.
Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography.
During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane.
These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.
最近有报道称，异氟烷在体内和体外均可增加大鼠纹状体中的多巴胺释放，且异氟烷可抑制大鼠脑突触体对多巴胺的摄取。然而，异氟烷对多巴胺能神经元的这些作用的功能意义尚不确定。伏隔核和纹状体内的多巴胺能机制在运动活动控制中起重要作用，多巴胺周转率的变化主要取决于多巴胺能神经元冲动流的变化。在本研究中，我们在小鼠的离散脑区中研究了异氟烷对运动活动和多巴胺周转率的影响。
将小鼠置于单独的气密透明塑料箱中，使其在25%氧气和75%氮气（新鲜气流，4升/分钟）中自主呼吸异氟烷。用Animex活动计测量运动活动。在给予或未给予异氟烷处理后将动物断头，通过高效液相色谱法测量不同脑区中单胺及其代谢物的浓度。
在停止20分钟异氟烷暴露后的10分钟内，吸入1.5%异氟烷的动物运动活动显著增加，但吸入0.7%异氟烷的动物则未增加。1.5%异氟烷引起的这种运动活动增加被低剂量的多巴胺受体拮抗剂氟哌啶醇（0.1毫克/千克）所消除。脑区单胺测定显示，1.5%异氟烷显著增加了伏隔核和纹状体中3,4-二羟基苯乙酸：多巴胺的比率（递质周转率的一个指标），但0.7%的浓度则未增加。在停止给予1.5%异氟烷后的20分钟内，这些区域中多巴胺周转率的显著增加持续存在。
这些结果表明，异氟烷诱导的苏醒期运动亢进可能与伏隔核和纹状体中多巴胺周转率增加有关。
