Minabe Y, Ashby C R
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Synapse. 1997 Feb;25(2):196-204. doi: 10.1002/(SICI)1098-2396(199702)25:2<196::AID-SYN10>3.0.CO;2-X.
In this study, we examined the effect of the acute and chronic administration of the selective neurokinin2 (NK2) receptor antagonist SR 48968 on the activity of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male rats. This was accomplished using the technique of in vivo, extracellular single cell recording. The intravenous (i.v.) administration of SR 48968 (10-1280 micrograms/kg) did not significantly alter the basal firing rate or pattern of either spontaneously active SNC or VTA DA neurons compared to control. However, the acute administration of 1 mg/kg, i.p., of SR 48968, but not its inactive enantiomer SR 48965, produced a significant increase in the number of spontaneously active DA cells in the SNC (48%) and VTA (28%) compared to vehicle controls. The i.p. administration of SR 48968 did not alter the basal firing pattern of either SNC or VTA DA neurons compared to vehicle controls. The pretreatment of animals with 1 mg/kg, i.p., of SR 48968 significantly potentiated the suppressant action of (+)-apomorphine on spontaneously active SNC and VTA DA cells. In contrast to its acute effects, the administration of 1 mg/kg, i.p. of SR 48968 once daily for 21 days produced a significant decrease in the number of spontaneously active DA cells in the SNC and VTA. The decrease in the number of spontaneously active VTA DA cells was not reversed by (+)-apomorphine administration in fact, a further decrease in the number of VTA DA cells was observed. This suggests that the SR 48968-induced decrease in the number of spontaneously active DA neurons may not be the result of depolarization block. Overall, these results suggest that the acute and chronic administration of SR 48968 alters the number of spontaneously active midbrain DA neurons in anesthetized rats.
在本研究中，我们检测了选择性神经激肽2（NK2）受体拮抗剂SR 48968急性和慢性给药对麻醉雄性大鼠黑质致密部（SNC）和腹侧被盖区（VTA）中自发活动的多巴胺（DA）细胞活性的影响。这是通过体内细胞外单细胞记录技术完成的。与对照组相比，静脉注射（i.v.）SR 48968（10 - 1280微克/千克）并未显著改变自发活动的SNC或VTA DA神经元的基础放电率或放电模式。然而，腹腔注射（i.p.）1毫克/千克的SR 48968，而非其无活性对映体SR 48965，与溶剂对照组相比，使SNC（48%）和VTA（28%）中自发活动的DA细胞数量显著增加。与溶剂对照组相比，腹腔注射SR 48968并未改变SNC或VTA DA神经元的基础放电模式。用1毫克/千克腹腔注射SR 48968对动物进行预处理，显著增强了（+）-阿扑吗啡对自发活动的SNC和VTA DA细胞的抑制作用。与其急性效应相反，每天腹腔注射1毫克/千克的SR 48968，持续21天，使SNC和VTA中自发活动的DA细胞数量显著减少。事实上，（+）-阿扑吗啡给药并未逆转自发活动的VTA DA细胞数量的减少，反而观察到VTA DA细胞数量进一步减少。这表明SR 48968诱导的自发活动DA神经元数量减少可能不是去极化阻滞的结果。总体而言，这些结果表明，SR 48968的急性和慢性给药改变了麻醉大鼠中脑自发活动的DA神经元数量。
