Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats
Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats
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DOI：
10.1007/s00210-009-0405-0
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发表时间：
2009-07-01
影响因子：
3.6
通讯作者：
Gomita, Yutaka
中科院分区：
文献类型：
--
作者：
Kitagawa, Kouhei;Kitamura, Yoshihisa;Gomita, Yutaka
多巴胺D2/D3受体激动剂普拉克索已被临床证明可改善抑郁症或难治性抑郁症。然而，多巴胺受体系统参与普拉克索对抑郁症的影响仍不清楚。我们研究了普拉克索对正常和促肾上腺皮质激素（ACTH）治疗大鼠强迫游泳试验期间不动持续时间的影响，并进一步分析了多巴胺受体在这种作用中的可能作用。此外，通过向内侧前额叶皮层和丘脑核中进行显微注射，特别探索了普拉克索在该模型中的作用机制与作用部位的关系。普拉克索（0.3-1 mg/kg）显著缩短了正常和ACTH处理大鼠的不动持续时间。在正常大鼠中，这种作用可被D2受体拮抗剂L-741，626和D3受体拮抗剂萘法多曲胺阻断。此外，在强迫游泳试验中，将普拉克索输注到内侧前额叶皮质而不是内侧前额叶皮质，降低了正常和ACTH治疗大鼠的不动性。综上所述，这些实验的结果表明，通过多巴胺能系统对ACTH处理的大鼠给予普拉克索（给予内侧前额叶皮质而非内侧前额叶皮质），可产生抗抑郁样作用。普拉克索的不动性降低作用可能由多巴胺D2和D3受体介导。
The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.