Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant actions of a selective serotonin reuptake inhibitor, fluoxetine
Autor: | Yong-Seok Oh, Paul Greengard, Takahide Shuto, Yong Kim, Tsuyoshi Miyakawa, Akinori Nishi, Jin Hyeok Jang, Mahomi Kuroiwa, Chang Hoon Shin, Yukie Kawahara, Yuuki Hanada, Yoshinori N. Ohnishi, Naoki Sotogaku |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Agonist Fluoxetine Cell biology medicine.drug_class business.industry Serotonin reuptake inhibitor Dentate gyrus Neurogenesis Pharmacology Article 03 medical and health sciences Cellular and Molecular Neuroscience Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine Dopamine receptor D1 Dopamine medicine Antidepressant business Molecular Biology 030217 neurology & neurosurgery medicine.drug Neuroscience |
Zdroj: | Molecular Psychiatry |
ISSN: | 1476-5578 1359-4184 |
Popis: | Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches. Here, we demonstrate that dopamine D1 receptors in the dentate gyrus act as a pivotal mediator of antidepressant actions in mice. Chronic administration of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, increases D1 receptor expression in mature granule cells in the dentate gyrus. The increased D1 receptor signaling, in turn, contributes to the actions of chronic fluoxetine treatment, such as suppression of acute stress-evoked serotonin release, stimulation of adult neurogenesis and behavioral improvement. Importantly, under severely stressed conditions, chronic administration of a D1 receptor agonist in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression and behavioral responses. Thus, our results suggest that stimulation of D1 receptors in the dentate gyrus is a potential adjunctive approach to improve therapeutic efficacy of SSRI antidepressants. |
Databáze: | OpenAIRE |
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