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- Title
3'-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway.
- Authors
Bai Li; Yangyang Hou; Ming Zhu; Hongkun Bao; Jun Nie; Zhang, Grace Y.; Liping Shan; Yao Yao; Kai Du; Hongju Yang; Meizhang Li; Bingrong Zheng; Xiufeng Xu; Chunjie Xiao; Jing Du
- Abstract
Background: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. Methods: We studied the antidepressant effects of 3'-deoxyadenosine (3'-dA, Cordycepin) and the critical role of the a-amino-3- hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3'-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. Results: We found that an injection of 3'-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45 min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3'-dA. Unlike the psycho-stimulants, 3'-dA did not show a hyperactive effect in the open field test. After 45 min or 5 days of treatment, 3'-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45 min of treatment, 3'-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3'-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3'-dA. Conclusion: This study identified 3'-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway.
- Subjects
DEOXYADENOSINE; ANTIDEPRESSANTS; EXCITATORY amino acid agents; PATHOLOGICAL physiology; PHOSPHORYLATION
- Publication
International Journal of Neuropsychopharmacology, 2016, Vol 19, Issue 4, p1
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1093/ijnp/pyv112