小鼠黑质纹状体多巴胺释放的突触前抑制：阿扑吗啡、GBL和CGS 10746B之间缺乏交叉耐受性。

Presynaptic inhibition of nigrostriatal dopamine release in the mouse: lack of cross tolerance between apomorphine, GBL and CGS 10746B.

作者信息

Wood P L, Altar C A, Kim H S

机构信息

Research Department, CIBA-GEIGY Corp., Summit, N.J. 07901.

出版信息

Life Sci. 1988;42(16):1503-6. doi: 10.1016/0024-3205(88)90006-9.

DOI:10.1016/0024-3205(88)90006-9

PMID:3352463

Abstract

Acute parenteral injections of apomorphine, gamma-butyrolactone (GBL) and CGS 10746B decreased dopamine release in the mouse nigrostriatal pathway as evidenced by decreases in striatal 3-methoxytyramine levels. In a 7 day treatment paradigm, the effects of acute apomorphine, GBL and CGS 10746B were unaltered in animals treated b.i.d. with GBL (500 mg/kg, i.p.). In contrast, the actions of acute CGS 10746B expressed a complete tolerance in mice treated b.i.d. with CGS 10746B (20 mg/kg, i.p.), while the actions of acute apomorphine or GBL were similar in the chronic saline and chronic CGS 10746 groups. These data show that the inhibition of striatal dopamine release by CGS 10746B is susceptible to tolerance. In addition, the lack of cross tolerance between GBL, apomorphine and CGS 10746B suggests independent sites of action for these agents in inhibiting dopamine release.

摘要

急性肠胃外注射阿扑吗啡、γ-丁内酯（GBL）和CGS 10746B可降低小鼠黑质纹状体通路中的多巴胺释放，纹状体3-甲氧基酪胺水平降低证明了这一点。在为期7天的治疗模式中，急性阿扑吗啡、GBL和CGS 10746B对每天腹腔注射GBL（500毫克/千克）的动物的作用未改变。相比之下，急性CGS 10746B的作用在每天腹腔注射CGS 10746B（20毫克/千克）的小鼠中表现出完全耐受性，而急性阿扑吗啡或GBL的作用在慢性生理盐水组和慢性CGS 10746组中相似。这些数据表明，CGS 10746B对纹状体多巴胺释放的抑制作用易产生耐受性。此外，GBL、阿扑吗啡和CGS 10746B之间缺乏交叉耐受性，表明这些药物在抑制多巴胺释放方面具有独立的作用位点。