Dopaminergic and serotonergic autoreceptor stimulation effects are equivalent and additive in the suppression of spontaneous and cocaine induced locomotor activity
Dopaminergic and serotonergic autoreceptor stimulation effects are equivalent and additive in the suppression of spontaneous and cocaine induced locomotor activity
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DOI：
10.1016/j.brainres.2004.05.091
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发表时间：
2004-09-03
期刊：
影响因子：
2.9
通讯作者：
Huston, JP
中科院分区：
文献类型：
--
作者：
Carey, RJ;DePalma, G;Huston, JP
我们使用低剂量范围的D-2受体激动剂阿扑吗啡（APO）和5-HT 1A受体激动剂8-OHDPAT（8 OH）来刺激自身受体，并以这种方式评估降低DA和5-HT活性对自发和可卡因诱导的运动行为的单独和组合效应。进行了两个单独的实验。在第一个实验中，用生理盐水、8 OH、APO或8 OH加APO（0.01、0.025、0.05 mg/kg）测试单独的大鼠组（N = 10）。在0.05 mg/kg剂量下，8 OH和APO诱导了相似的自发活动剂量相关性降低（高达约50%）。8 OH加APO联合给药诱导了剂量相关的运动减少（约90%）。在0.05 mg/kg剂量水平下，分别给予的药物处理阻断了可卡因诱导的活性增加，8 OH和APO抑制作用再次叠加。在第二个实验中，单独的组（N = 10）接受生理盐水、0.05 mg/kg APO、0.05 mg/kg 8 OH或0.05 mg/kg APO加0.05 mg/kg 8 OH。如在第一个实验中，分别给予的8 OH和APO使自发活动减少约50%，当一起给予时，自发活动几乎被消除（减少80-90%）。当联合APO/8 OH组也接受5-HT 1A拮抗剂WAY 100635（0.05 mg/kg）时，对活性的影响相当于单独0.05 mg/kg APO。离体多巴胺（DA）和5-羟色胺（5-HT）代谢的神经化学测量证实，APO降低DA周转，8 OH降低5-HT周转，并且联合治疗降低DA和5-HT周转。因此，对于自发和可卡因诱导的运动行为，低剂量8 OH和APO处理抑制运动活性，并且这些作用是累加的。这些结果表明，DA和5-HT系统分别有助于运动激活。这些结果表明，重要的是要考虑DA和5-HT的贡献，如帕金森氏病的运动障碍，以及多动状态，如兴奋剂药物引起的。(C)2004 Elsevier B. V.保留所有权利。
We used the D-2 receptor agonist, apomorphine (APO) and the 5-HT1A receptor agonist, 8-OHDPAT (8OH) in a low dose range to stimulate autoreceptors and in this way assess the separate and combined effects of reduced DA and 5-HT activity upon spontaneous and cocaine induced locomotor behavior. Two separate experiments were conducted. In the first experiment, separate groups of rats (N = 10) were tested with either saline, 8OH, APO or 8OH plus APO (0.01, 0.025, 0.05 mg/kg). At 0.05 mg/kg, 8OH and APO induced similar dose related decreases (up to approximately 50%) in locomotor activity. The combined 8OH plus APO treatment induced dose-related decreases in locomotion (approximately 90%). At the 0.05 mg/kg dose level, the drug treatments given separately blocked cocaine induced increases in activity and the 8OH and APO inhibitory effects were again additive. In the second experiment, separate groups (N = 10) received saline, 0.05 mg/kg APO, 0.05 mg/kg 8OH or 0.05 mg/kg APO plus 0.05 mg/kg 8OH. As in the first experiment, the 8OH and APO given separately reduced locomotor activity by approximately 50% and when given together, locomotor activity was virtually eliminated (reduced 80-90%). When the combined APO/8OH group also received the 5-HT1A antagonist, WAY 100635 (0.05 mg/kg), the effect on activity was equivalent to 0.05 mg/kg APO alone. Ex vivo neurochemical measurement of dopamine (DA) and serotonin (5-HT) metabolism confirmed that the APO decreased DA turnover, 8OH decreased 5-HT turnover and the combined treatment reduced both the DA and 5-HT turnover. Thus, for both spontaneous and cocaine induced locomotor behavior, the low dose 8OH and APO treatments suppressed locomotor activity and these effects were additive. These findings indicate that DA and 5-HT systems contribute separately to motoric activation. These results suggest that it is important to consider both DA and 5-HT contributions to disorders of motoric impoverishment such as Parkinson's disease as well as to hyperkinetic states such as those induced by stimulant drugs. (C) 2004 Elsevier B.V. All rights reserved.