Ono M, Watanabe A, Matsumoto Y, Fukushima T, Nishikawa Y, Moriya T, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Neuroscience. 1996 May;72(1):213-24. doi: 10.1016/0306-4522(95)00500-5.
We examined whether methamphetamine modifies the photic entraining responses in the rat suprachiasmatic nucleus. Optic nerve stimulation increased vasoactive intestinal polypeptide release from rat suprachiasmatic nucleus slices, and methamphetamine inhibited this increase in a concentration-dependent manner. Optic nerve stimulation has been reported to evoke field potentials in rat suprachiasmatic nucleus slices. Methamphetamine attenuated this field potential, and maximal inhibition (75.5%) was achieved at a concentration of 100 microM. Systemic administration of methamphetamine (1-5 mg/kg) inhibited light (300 lux, 1h)-induced Fos expression in the suprachiasmatic nucleus; methamphetamine at a dose of 5 mg/kg, i.p. caused 40% inhibition of light-induced Fos expression. We examined whether the inhibitory effect of methamphetamine on photic entraining responses mediates serotonin release from the suprachiasmatic nucleus. High-performance liquid chromatographic analysis revealed that methamphetamine application increased serotonin release from rat suprachiasmatic nucleus slices in a concentration-dependent manner, but did not affect noradrenaline release. In addition, reduction of serotonin content attenuated the effect of methamphetamine on field potential induced by optic nerve stimulation in vitro and also light-induced phase advances of wheel running activity rhythm in vivo. The present results support the idea that methamphetamine produces an inhibitory effect on photic entrainment in the suprachiasmatic nucleus via serotonin release.
我们研究了甲基苯丙胺是否会改变大鼠视交叉上核中的光诱导同步反应。视神经刺激可增加大鼠视交叉上核切片中血管活性肠肽的释放，而甲基苯丙胺能以浓度依赖的方式抑制这种增加。据报道，视神经刺激可在大鼠视交叉上核切片中诱发场电位。甲基苯丙胺可减弱这种场电位，在浓度为100微摩尔时可达到最大抑制率（75.5%）。全身注射甲基苯丙胺（1-5毫克/千克）可抑制光（300勒克斯，1小时）诱导的视交叉上核中Fos蛋白的表达；腹腔注射5毫克/千克的甲基苯丙胺可导致光诱导的Fos蛋白表达受到40%的抑制。我们研究了甲基苯丙胺对视交叉上核光诱导同步反应的抑制作用是否通过5-羟色胺从视交叉上核的释放来介导。高效液相色谱分析显示，应用甲基苯丙胺可使大鼠视交叉上核切片中5-羟色胺的释放以浓度依赖的方式增加，但不影响去甲肾上腺素的释放。此外，降低5-羟色胺含量可减弱甲基苯丙胺对体外视神经刺激诱导的场电位的影响，以及对体内光诱导的轮转活动节律相位提前的影响。目前的结果支持这样一种观点，即甲基苯丙胺通过5-羟色胺的释放对视交叉上核中的光同步产生抑制作用。
