Chronic imipramine downregulates cyclic AMP signaling in rat hippocampus.
Chronic imipramine downregulates cyclic AMP signaling in rat hippocampus.
复制标题
慢性丙咪嗪下调大鼠海马中的环 AMP 信号传导。
DOI：
10.1097/wnr.0b013e328321b5a0
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发表时间：
2009
期刊：
影响因子：
1.7
通讯作者：
Wong,Ma-Li
中科院分区：
文献类型：
--
作者：
Reierson,GillianW;Mastronardi,ClaudioA;Licinio,Julio;Wong,Ma-Li
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are synthesized by adenylate cyclase and guanylyl cyclase and degraded by phosphodiesterases. Antidepressant treatment action is hypothesized to occur through increased cAMP signaling; however, antidepressants are also reported to increase phosphodiesterase-4 expression. We addressed this paradox by systematically studying elements of intracellular signaling in the hippocampus of rats chronically treated with imipramine. We observed decreases in cAMP levels, which were congruent with our findings of increased gene expression for phosphodiesterases and decreased adenylate cyclase. Immunoassay results showed unchanged cGMP and brain-derived neurotrophic factor levels. We conclude that in contrast with the assumption of antidepressant-mediated increases in cAMP levels, long-term imipramine treatment may have the opposite effect, namely decreased hippocampal cAMP.
