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 D₂ agonist quinelorane, or pretreated with the selective D₁ antagonist SCH23390 in combination with the selective D₂ antagonist sulpiride or D₃ antagonist SB277011A. Body temperature, which is regulated by the hypothalamic dopaminergic system, was monitored to evaluate changes in the dopaminergic system of the hypothalamus. DA D₂ receptor (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.

啮齿类动物的嗅球切除术 (OBX) 诱导神经化学和行为变化，类似于在患有抑郁症的个体中观察到的变化。我们之前的研究表明 OBX 改变了小鼠纹状体中的多巴胺能功能；然而，对下丘脑多巴胺能功能的影响尚不清楚。因此，在这项研究中，我们检查了 OBX 后下丘脑的多巴胺能系统变化。给小鼠施用非选择性多巴胺 (DA) 激动剂阿扑吗啡或选择性 D ₂激动剂喹诺兰，或用选择性 D ₁拮抗剂 SCH23390 联合选择性 D ₂拮抗剂舒必利或 D ₃预处理拮抗剂 SB277011A。由下丘脑多巴胺能系统调节的体温被监测以评估下丘脑多巴胺能系统的变化。大 D ₂通过蛋白质印迹评估下丘脑中受体 (D2DR)、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的阿扑吗啡诱导或喹诺兰诱导的体温过低。阿扑吗啡诱导的体温过低反应被舒必利逆转，但 SCH23390 或 SB277011A 没有逆转。此外，OBX 小鼠下丘脑中的 TH 和 p-DARPP-32 水平降低，D2DR 增加。这些发现表明，OBX 小鼠表现出与下丘脑相关的增强的 DA 受体反应性，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。