Abstract | INTRODUCTION:
Binge eating disorder (BED) is associated with dopaminergic activation as food reward, resulting in metabolism-related disorders. Stimulation of angiotensin type 2 (AT2) receptor is reported to inhibit dopamine synthesis. We investigated the possible roles of AT2 receptor-mediated dopamine regulation in the pathogenesis of BED. MATERIALS AND METHODS: Male C57BL/6 mice, type 2 diabetic (KKAy) mice and AT2 receptor-null (AT2KO) mice at eight weeks old were treated with AT2 receptor agonist, compound 21 ( C21) or saline for two weeks. Mice were subjected to fasting for two days followed by re-feeding for seven days. RESULTS: Treatment with C21 attenuated the rebound proportion of body weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT2KO mice. Dopamine concentration in the striatum was further increased by fasting in KKAy and AT2KO mice. Administration of C21 significantly attenuated this fasting-induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2 expression in the substantia nigra were markedly lower in KKAy mice compared with C57BL/6 mice, while administration of C21 increased their expression in KKAy mice. CONCLUSIONS: Our study suggests that AT2 receptor stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance.
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Authors | Hirotomo Nakaoka, Masaki Mogi, Harumi Kan-No, Kana Tsukuda, Kousei Ohshima, Xiao-Li Wang, Toshiyuki Chisaka, Hui-Yu Bai, Bao-Shuai Shan, Masayoshi Kukida, Jun Iwanami, Masatsugu Horiuchi |
Journal | Journal of the renin-angiotensin-aldosterone system : JRAAS
(J Renin Angiotensin Aldosterone Syst)
Vol. 16
Issue 4
Pg. 749-57
(Dec 2015)
ISSN: 1752-8976 [Electronic] England |
PMID | 25757658
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2015. |
Chemical References |
- Receptor, Angiotensin, Type 2
- Receptors, Dopamine
- Dopamine
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Topics |
- Animals
- Behavior, Animal
- Binge-Eating Disorder
(metabolism)
- Blood Pressure
- Brain
(metabolism)
- Diabetes Mellitus, Experimental
(metabolism, pathology)
- Dopamine
(metabolism)
- Fasting
- Gene Deletion
- Immunohistochemistry
- Male
- Mice, Inbred C57BL
- Neostriatum
(metabolism)
- Receptor, Angiotensin, Type 2
(metabolism)
- Receptors, Dopamine
(metabolism)
- Signal Transduction
- Systole
- Weight Gain
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