Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice
Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice
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嗅球切除小鼠下丘脑多巴胺 D2 受体超敏性
DOI：
10.1016/j.brainres.2020.147015
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Tan-No Koichi
中科院分区：
文献类型：
--
作者：
Takahashi Kohei;Nakagawasai Osamu;Nakajima Takeharu;Okubo Myu;Nishimura Yuki;Sakuma Wakana;Yamagata Ryota;Nemoto Wataru;Miyagawa Kazuya;Kurokawa Kazuhiro;Mochida-Saito Atsumi;Tsuji Minoru;Takeda Hiroshi;Tadano Takeshi;Tan-No Koichi
嗅球切除术（OBX）在啮齿类动物诱导神经化学和行为的变化类似于在抑郁症患者中观察到的。我们先前的研究表明OBX改变小鼠纹状体中的多巴胺能功能;然而，对下丘脑中多巴胺能功能的影响尚不清楚。因此，在这项研究中，我们研究了多巴胺能系统的变化，在下丘脑OBX后。给小鼠注射非选择性多巴胺（DA）受体激动剂阿扑吗啡或选择性D2受体激动剂奎诺烷，或预先用选择性D1受体拮抗剂SCH 23390联合选择性D2受体拮抗剂舒必利或D3受体拮抗剂SB 277011 A处理。监测由下丘脑多巴胺能系统调节的体温，以评价下丘脑多巴胺能系统的变化。用蛋白质印迹法检测下丘脑DA D2受体（D2 DR）、酪氨酸羟化酶（TH）和磷酸化（p）- DA和cAMP调节的磷蛋白-32（DARPP-32）水平。OBX小鼠表现出显着增强阿扑吗啡诱导或奎诺烷诱导的体温过低。阿扑吗啡诱导的低温反应被舒必利逆转，但不是SCH 23390或SB 277011 A。此外，在OBX小鼠的下丘脑中，TH和p-DARPP-32水平降低，D2 DR增加。这些发现表明，OBX小鼠显示与下丘脑相关的DA受体反应性增强，这可能与该动物模型中报告的一些行为和神经化学改变有关。确定OBX小鼠下丘脑多巴胺能系统的变化可能为开发新的抗抑郁治疗提供有用的信息。
Olfactory bulbectomy (OBX) in rodents induces neurochemical and behavioral changes similar to those observed in individuals with depressive disorders. Our previous study suggested that OBX alters dopaminergic function in the striatum of mice; however, the effects on dopaminergic function in the hypothalamus is unknown. Therefore, in this study we examined dopaminergic system changes in the hypothalamus after OBX. Mice were administrated either the nonselective dopamine (DA) agonist apomorphine or the selective D2agonist quinelorane, or pretreated with the selective D1antagonist SCH23390 in combination with the selective D2antagonist sulpiride or D3antagonist SB277011A. Body temperature, which is regulated by the hypothalamic dopaminergic system, was monitored to evaluate changes in the dopaminergic system of the hypothalamus. DA D2receptor (D2DR), tyrosine hydroxylase (TH), and phosphorylated (p)- DA- and cAMP-regulated phosphoprotein-32 (DARPP-32) levels in the hypothalamus were evaluated by western blotting. OBX mice exhibited significantly enhanced apomorphine-induced or quinelorane-induced hypothermia. The apomorphine-induced hypothermic response was reversed by the administration of sulpiride, but not SCH23390 or SB277011A. Moreover, TH and p-DARPP-32 levels were reduced and D2DR increased in the hypothalamus of OBX mice. These findings revealed that the OBX mice display enhanced DA receptor responsiveness associated with the hypothalamus, which may relate to some of the behavioral and neurochemical alterations reported in this animal model. Identification of changes in the hypothalamic dopaminergic system of OBX mice may provide useful information for the development of novel antidepressant treatments.