Rosengarten H, Friedhoff A J
Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, NY 10016, USA.
Biol Psychiatry. 1998 Dec 1;44(11):1178-84. doi: 10.1016/s0006-3223(98)00017-1.
We have demonstrated that rats injected with D1 agonists SKF 38393 or A68930 demonstrate repetitive jaw movements (RJM). These agonist-induced movements in rats are similar in their appearance to those induced in rats by long-term treatment with antipsychotic drugs. Over recent years D-1 receptors were discovered which showed linkage not only to c-AMP but also to PI hydrolysis. We examined the effect of EEDQ inactivation of D1 receptors on D-1 mediated PI hydrolysis and RJM.
Twenty four hours following EEDQ or vehicle administration D-1 agonists or vehicle were administered. The number of RJM episodes was assessed in EEDQ and vehicle treated rats. D-1 receptor density and inositol phosphate formation were determined in the striata.
EEDQ administration resulted, 24 hours later, in 70-80% selective depletion of D-1 receptors in the striata but did not modify the rate of RJM induced by D-1 agonists. There was no significant difference in D-1 mediated PI hydrolysis in EEDQ treated rats when compared to vehicle treated group.
The present data support the earlier demonstration of D-1 agonist induced RJM, an effect mediated by a subpopulation of a D-1 receptor subtype and constitute the first behavioral evidence for the existence of a behavioral response mediated by D-1 like dopamine receptors linked to an alternate second messenger system-PI hydrolysis.
我们已经证明,注射D1激动剂SKF 38393或A68930的大鼠会出现重复性下颌运动(RJM)。这些激动剂在大鼠中诱导的运动,其外观与长期使用抗精神病药物诱导的运动相似。近年来发现了D-1受体,它不仅与c-AMP有关联,还与磷脂酰肌醇(PI)水解有关。我们研究了D1受体的EEDQ失活对D-1介导的PI水解和RJM的影响。
在给予EEDQ或赋形剂24小时后,给予D-1激动剂或赋形剂。评估EEDQ处理组和赋形剂处理组大鼠的RJM发作次数。测定纹状体中的D-1受体密度和肌醇磷酸的形成。
给予EEDQ 24小时后,纹状体中D-1受体选择性耗竭70 - 80%,但并未改变D-1激动剂诱导的RJM速率。与赋形剂处理组相比,EEDQ处理组大鼠中D-1介导的PI水解没有显著差异。
目前的数据支持了早期关于D-1激动剂诱导RJM的证明,这一效应由D-1受体亚型的一个亚群介导,并且构成了由与另一种第二信使系统——PI水解相关的D-1样多巴胺受体介导的行为反应存在的首个行为学证据。