Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr 3;50:116-24. doi: 10.1016/j.pnpbp.2013.12.011. Epub 2013 Dec 26.
Cumulative studies indicated that adult hippocampal neurogenesis might be involved in the action mechanism of antidepressant drugs and/or the pathophysiology of depression. Dopamine (DA) is involved in the regulation of motivation, volition, interest/pleasure, and attention/concentration, all of which are likely to be impaired in depressed patients. Several previous reports suggest that depression may often be accompanied by a relative hypo-dopaminergic state, and some DA receptor agonists are beneficial effects in the treatment for refractory and bipolar depression. In the present study, to clarify the direct effect of DA on neural progenitor cells, we examined the effect of DA on the proliferation of adult rat dentate gyrus-derived neural precursor cells (ADPs). In addition, we examined the effect of DA receptor agonists on adult rat hippocampal neurogenesis in vivo. Results showed that DA promoted the increase of ADPs via D1-like receptor and D1-like receptor agonist promoted the survival of newborn cells in the adult hippocampus. On the contrary, D2-like receptor agonist did not affect both proliferation and survival. These results suggested that DA might play, at least in part, a role in adult hippocampal neurogenesis via D1-like receptor and the activation of D1-like receptor has a therapeutic potential for depression.
累积研究表明，成年海马神经发生可能参与抗抑郁药物的作用机制和/或抑郁症的病理生理学。多巴胺（DA）参与调节动机、意志、兴趣/愉悦以及注意力/集中力，而这些都可能在抑郁症患者中受到损害。一些先前的报告表明，抑郁症可能经常伴随着相对的低多巴胺能状态，一些 DA 受体激动剂对治疗难治性和双相抑郁症有有益的效果。在本研究中，为了阐明 DA 对神经祖细胞的直接作用，我们研究了 DA 对成年大鼠齿状回源性神经前体细胞（ADPs）增殖的影响。此外，我们还研究了 DA 受体激动剂对成年大鼠海马神经发生的体内作用。结果表明，DA 通过 D1 样受体促进 ADP 的增加，D1 样受体激动剂促进成年海马中新细胞的存活。相反，D2 样受体激动剂既不影响增殖也不影响存活。这些结果表明，DA 可能至少部分通过 D1 样受体在成年海马神经发生中发挥作用，D1 样受体的激活对抑郁症具有治疗潜力。
