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Phosphodiesterase 4 inhibitors enhance sexual pleasure-seeking activity in rodents.

机译:磷酸二酯酶4抑制剂增强了啮齿动物的性快感活动。

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摘要

Pleasure-seeking deficits, including lack of libido, are a core feature of depression. Animal and preliminary clinical studies both suggest that phosphodiesterase 4 (PDE4) is a target for developing novel antidepressants. This study examined the potential involvement of PDE4 in the pathology of depression in both animal models and human postmortem brains. In humans, PDE4B and PDE4D levels were elevated in cingulate cortical tissue from individuals with major depressive disorder (MDD) compared to controls. Using the female urine smelling test (FUST), a recently refined method for monitoring sexual pleasure-seeking activity in mice, we found that icv infusion of selective potent PDE4 inhibitors enhanced sexual pleasure-seeking activity in male mice that underwent the learned helplessness or serotonin depletion paradigms. The infusion also increased sexual pleasure-seeking activity in naive male mice. The results suggest that PDE4 may be a plausible contributor to the sexual pleasure-seeking deficits seen in depressed patients; inhibiting PDE4 may restore these deficits.
机译:包括缺乏性欲在内的寻求愉悦性缺陷是抑郁症的核心特征。动物和初步临床研究均表明,磷酸二酯酶4(PDE4)是开发新型抗抑郁药的靶标。这项研究检查了PDE4在动物模型和人类死后大脑抑郁症病理中的潜在参与。在人类中,与重度抑郁症(MDD)个体相比,扣带回皮质组织中的PDE4B和PDE4D水平升高。使用雌性尿味测试(FUST),这是一种最近改进的监测小鼠性快感活动的方法,我们发现icv选择性强效PDE4抑制剂的输注可增强患有习得性无助或血清素的雄性小鼠的性快感活动。耗竭范式。输注还增加了幼稚雄性小鼠的性快感活动。结果表明,PDE4可能是抑郁症患者中性快感缺陷的合理原因。抑制PDE4可以恢复这些缺陷。

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