Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice

• Published in: Brain research Vol. 1746; p. 147015
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2020
• Subjects: Depression; Dopamine; Hypothalamus; Olfactory bulbectomy; Tyrosine hydroxylase; D2DR; Dopamine; OBX; TBST; CPu; DARPP-32; s.c; Depression; HPA axis; i.p; Tyrosine hydroxylase; Hypothalamus; AUC; ECL; NAcSh; p; TH; ANOVA; NAcC; SEM; Olfactory bulbectomy; DA
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2020.147015

•Sulpiride reversed apomorphine-induced hypothermic response in OBX mice.•SCH23390 and SB277011A failed to reverse apomorphine-induced hypothermia.•OBX mice exhibited significantly enhanced quinelorane-induced hypothermia.•OBX mice showed reduced in TH and p-DARPP-32 levels in the hypothalamus.•OBX mice showed increased D2DR in the hypothalamus. 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.