Related Experiment Video
Updated: Dec 14, 2025
Olfactory Assays for Mouse Models of Neurodegenerative Disease
Published on: August 25, 2014
Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice
Kohei Takahashi1, Osamu Nakagawasai2, Takeharu Nakajima2
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan; Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
Abstract:
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.
Insights
Olfactory bulbectomy in mice enhances hypothalamic dopamine D2 receptor responsiveness, indicated by altered body temperature regulation. These changes in the dopaminergic system may inform new antidepressant treatments.
Area of Science:
- Neuroscience
- Neuropharmacology
- Endocrinology
Background:
- Olfactory bulbectomy (OBX) in rodents mimics depressive disorder symptoms.
- Previous research indicated OBX impacts striatal dopaminergic function.
- The effect of OBX on hypothalamic dopaminergic function remained unexplored.
Purpose of the Study:
- To investigate alterations in the hypothalamic dopaminergic system following OBX.
- To assess the functional changes in dopamine receptor activity in the hypothalamus.
Main Methods:
- OBX was performed on mice.
- Mice received dopamine agonists (apomorphine, quinelorane) or antagonists (SCH23390, sulpiride, SB277011A).
- Body temperature, hypothalamic dopamine D2 receptor (D2DR), tyrosine hydroxylase (TH), and p-DARPP-32 levels were measured.
Main Results:
- OBX mice showed heightened hypothermic responses to dopamine agonists.
- Sulpiride reversed the hypothermic effect, unlike other antagonists.
- Hypothalamic TH and p-DARPP-32 levels decreased, while D2DR levels increased post-OBX.
Conclusions:
- OBX induces enhanced hypothalamic dopamine receptor responsiveness.
- These neurochemical and functional changes in the hypothalamus may contribute to depression-like behaviors.
- Findings offer insights for developing novel antidepressant therapies targeting the hypothalamic dopaminergic system.
