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
Jazyk: angličtina
Rok vydání: 2018
Předmět:
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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