Irifune M, Sato T, Kamata Y, Nishikawa T, Nomoto M, Fukuda T, Kawahara M
Department of Pharmacology, Kagoshima University Dental School, Japan.
Can J Anaesth. 1998 May;45(5 Pt 1):471-8. doi: 10.1007/BF03012584.
To investigate the effects of the benzodiazepine diazepam on ketamine-induced hyperlocomotion and dopamine turnover.
Adult male ddY mice were used (n = 218). Locomotor activity was measured with four circular activity cages equipped with three photocell sensor units. Interruptions by a mover of the infrared light Peams were recorded on electromechanical counters, and automatically printed every 10 min for three hours after the ketamine injection. All drugs were administered intraperitoneally (i.p.). The concentrations of dopamine and its metabolites in discrete brain regions were measured by high performance liquid chromatography with electrochemical detection.
Ketamine (30 mg.kg-1) increased total locomotor activity counts for three hours to 442% of control in mice (P = 0.0001). Diazepam, 3 and 10 mg.kg-1, inhibited, in a dose-dependent fashion, this ketamine-induced hyperlocomotion by 26% (P = 0.0111) and 59% (P = 0.0001), respectively. Regional brain dopamine assays revealed that ketamine (30 mg.kg-1) increased the homovanillic acid:dopamine ratio (one indicator of dopamine turnover) to 121% of control in the nucleus accumbens (P = 0.0065) and to 111% in the striatum (P = 0.0135) at peak locomotion. Diazepam, 3 and 10 mg.kg-1, returned this increase in dopamine turnover produced by ketamine to control levels both in the nucleus accumbens (P = 0.0061 and P = 0.0117, respectively) and in the striatum (P = 0.0004 and P = 0.0047, respectively).
These results suggest that the inhibition by diazepam of ketamine-induced hyperlocomotion may be related to its ability to suppress the activation of dopamine neurons in the nucleus accumbens and striatum.
研究苯二氮䓬类药物地西泮对氯胺酮诱导的运动亢进及多巴胺代谢的影响。
选用成年雄性ddY小鼠（n = 218）。使用配备三个光电传感器单元的四个圆形活动笼测量运动活性。移动者对红外光束的干扰记录在机电计数器上，并在注射氯胺酮后的三小时内每10分钟自动打印一次。所有药物均通过腹腔注射（i.p.）给药。采用高效液相色谱电化学检测法测定不同脑区多巴胺及其代谢产物的浓度。
氯胺酮（30 mg·kg-1）使小鼠的总运动活性计数在三小时内增加至对照的442%（P = 0.0001）。3和10 mg·kg-1的地西泮以剂量依赖方式抑制这种氯胺酮诱导的运动亢进，分别抑制了26%（P = 0.0111）和59%（P = 0.0001）。脑区多巴胺检测显示，氯胺酮（30 mg·kg-1）在运动高峰时使伏隔核中的高香草酸：多巴胺比率（多巴胺代谢的一个指标）增加至对照的121%（P = 0.0065），纹状体中增加至111%（P = 0.0135）。3和10 mg·kg-1的地西泮使氯胺酮引起的多巴胺代谢增加在伏隔核（分别为P = 0.0061和P = 0.0117）和纹状体（分别为P = 0.0004和P = 0.0047）中恢复至对照水平。
这些结果表明，地西泮对氯胺酮诱导的运动亢进的抑制作用可能与其抑制伏隔核和纹状体中多巴胺神经元激活的能力有关。
