Anxiolytic- and antidepressant-like effects of 7-OH-DPAT, preferential dopamine D3 receptor agonist, in rats.

Polish journal of pharmacology Pub Date : 2004-09-01
Z Rogóz, G Skuza, A Kłlodzińska
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Abstract

The aim of the present study was to examine a potential anxiolytic- and antidepressant-like action of (+)-7-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (7-OH-DPAT), a preferential dopamine D(3) receptor agonist, and N-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl}-2-naphthylcarboxamide (BP 897), a partial dopamine D(3) receptor agonist, in male Wistar rats. Diazepam or imipramine were used as reference compounds. The anxiolytic-like effect of those drugs was tested in the elevated plus-maze test. The antidepressant-like effect was estimated using the forced swimming test. The obtained results showed that 7-OH-DPAT at low doses and BP 897 (like diazepam) induced anxiolytic-like effects in the elevated plus-maze test. 7-OH-DPAT, BP 897 and diazepam, tested at the doses effective in the model of anxiolytic-like actions, did not affect motor coordination. Moreover, 7-OH-DPAT at higher doses, like imipramine, showed antidepressant-like effect, significantly reducing immobility time in the forced swimming test. Combined treatment with 7-OH-DPAT and imipramine induced a stronger effect in Porsolt's test than administration of either drug alone, but did not increase the locomotor activity. In contrast, BP 897 was inactive in the forced swimming test when given alone but it potentiated the antidepressant-like effect of imipramine. These data suggest that preferential D(3) receptor agonists may play a role in the therapy of anxiety and/or depression, however, further studies are necessary to elucidate the mechanism of these actions.

优先多巴胺D3受体激动剂7-OH-DPAT在大鼠中的抗焦虑和抗抑郁样作用。
本研究的目的是研究多巴胺D(3)受体优先激动剂(+)-7-羟基-2-(二正丙胺)四溴化萘(7-OH-DPAT)和部分多巴胺D(3)受体激动剂N-{4-[4-(2-甲氧基苯基)-1-哌嗪基]丁基}-2-萘基carboxamide (BP 897)在雄性Wistar大鼠中的潜在抗焦虑和抗抑郁作用。以安定或丙咪嗪为对照物。这些药物的抗焦虑样作用在升高+迷宫试验中进行了测试。使用强迫游泳试验估计抗抑郁样效果。结果显示,低剂量7-OH-DPAT和BP 897(类似地西泮)在升高的+迷宫试验中诱导了抗焦虑样作用。7-OH-DPAT、BP 897和地西泮在抗焦虑样行为模型中有效的剂量不影响运动协调。此外,高剂量的7-OH-DPAT,如丙咪嗪,表现出类似抗抑郁的作用,在强迫游泳试验中显著减少静止时间。7-OH-DPAT和丙咪嗪联合治疗在Porsolt试验中的作用比单独用药更强,但没有增加运动活性。单独给药时,BP 897在强迫游泳试验中无活性,但增强了丙咪嗪的抗抑郁样作用。这些数据表明,优先D(3)受体激动剂可能在焦虑和/或抑郁的治疗中发挥作用,然而,需要进一步的研究来阐明这些作用的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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