Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats
Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats
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DOI：
10.1016/j.ejphar.2009.06.029
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发表时间：
2009-08-15
影响因子：
5
通讯作者：
Olivier, Berend
中科院分区：
文献类型：
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作者：
Breuer, Megan E.;Groenink, Lucianne;Olivier, Berend
多巴胺D-3/D-2受体激动剂普拉克索治疗可减轻帕金森病患者的抑郁症状。为了检测普拉克索的推定抗抑郁质量，在最有吸引力的抑郁症动物模型之一，嗅球切除（OBX）大鼠中评估了其作用。两项实验研究了普拉克索对球切除术诱导的多动症的影响。在实验I中。以0.3和1.0 mg/kg的剂量与参比多巴胺D-3受体激动剂7-OH-DPAT（0.1 mg/kg）和三环抗抑郁剂丙咪嗪（10 mg/kg）一起测试普拉克索。在实验II中，使用相同的参比化合物，以较低剂量（0.03和0.1 mg/kg）检测了普拉克索。所有动物在第1天（急性）在开放场地进行试验。普拉克索在（亚）慢性给药后（如丙咪嗪和7-OH-DPAT）而非急性给药后（如丙咪嗪和7-OH-DPAT）以U形剂量反应降低了球切除术诱导的活动过度。在治疗期间，最高剂量的普拉克索（1.0 mg/kg）未降低OBX活动过度。然而.停止治疗一周后，所有的普拉克索（包括1.0mg/kg剂量）、7-OH-DPAT和丙咪嗪组显示出OBX诱导的活动过度减少。普拉克索和7-OH-DPAT在OBX-大鼠模型中发挥抗抑郁作用，使（亚）慢性治疗期间球切除术诱导的活动过度正常化。此外，这两种化合物的治疗诱导了类似于已建立的抗抑郁药的球切除大脑的持久变化，强烈预测了重度抑郁症的抗抑郁活性。(C)2009爱思唯尔有限公司版权所有。
Treatment with pramipexole, a dopamine D-3/D-2 receptor agonist, reduces depressive symptoms in patients suffering from Parkinson's disease. To test the putative antidepressant quality of pramipexole, its effects were assessed in one of the most attractive animal models of depression, the olfactory bulbectomized (OBX) rat. Two experiments studied the effects of pramipexole on bulbectomy-induced hyperactivity. In experiment I. pramipexole was tested at 0.3 and 1.0 mg/kg together with the reference dopamine D-3 receptor agonist 7-OH-DPAT (0.1 mg/kg) and the tri-cyclic antidepressant imipramine (10 mg/kg). In experiment II, pramipexole was tested at lower doses: 0.03 and 0.1 mg/kg, with the same reference compounds. All animals were tested in the open field on days one (acute). seven (sub-chronic) and fourteen (chronic) of administration, as well as one week after cessation of treatment.Pramipexole, in a U-shaped dose response, reduced bulbectomy-induced hyperactivity after (sub) chronic but not acute administration (like imipramine and 7-OH-DPAT). The highest dose of pramipexole (1.0 mg/kg) did not reduce OBX hyperactivity during treatment. However. one week after cessation of treatment, all pramipexole (including the 1.0 mg/kg dose), 7-OH-DPAT and imipramine groups showed a reduction in OBX-induced hyperactivity. Pramipexole and 7-OH-DPAT exert an antidepressant profile in the OBX-rat model in normalizing bulbectomy-induced hyperactivity during (sub) chronic treatment. Moreover, treatment with both these compounds induced long-lasting changes in the bulbectomized brain similar to established antidepressants, strongly predicting antidepressant activity in major depression. (C) 2009 Elsevier B.V. All rights reserved.