Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect
Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect
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DOI：
10.1016/s0006-3223(00)01114-8
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发表时间：
2001-05-01
影响因子：
10.6
通讯作者：
Duman, RS
中科院分区：
文献类型：
--
作者：
Chen, ACH;Shirayama, Y;Duman, RS
背景资料：最近的研究表明，慢性抗抑郁治疗增加了环腺苷酸（cAMP）反应元件结合蛋白（CREB）在mt海马的表达。本研究旨在确定CREB是否是产生抗抑郁样作用的相关靶点。方法：我们采用单纯疱疹病毒（HSC）介导的基因转移技术过表达CREB，并确定其对习得性无助和强迫游泳试验的影响，这两个模型用于抗抑郁药物的药理学筛选。结果：在习得性无助模型中，双侧齿状回微量注射HSV-CREB的大鼠在随后的条件回避休息中的逃避失败次数显著少于注射对照载体（HSV-LacZ）的大鼠。在强迫游泳实验中，海马CA 1锥体细胞层或前额叶皮质内微量注射HSV-CREB均能产生抗抑郁反应。与注射HSV-LacZ相比，齿状回CREB的表达显著缩短了不动时间。这些结果表明，过度-CREB在海马中的表达导致抗抑郁作用，并提示CREB可能作为新型治疗剂的潜在分子靶点。(C)2001生物精神病学学会。
Background: Recent studies that demonstrated that chronic antidepressant treatment increases the expression of the cyclic amp (cAMP) response element binding protein (CREB) in mt hippocampus. The study presented here was conducted to determine if CREB is a relevant target that produces an antidepressant-like effect.Methods: We employed the herpes simple virus (HSC)-mediated gene transfer technique to overexpress CREB and determined its effect on the learned helplessness and forced swim tests, two established models used for pharmacological screening of antidepressant drugs.Results: in the learned helplessness model, rats that received bilateral microinjection of HSV-CREB into the dentate gyrus showed significantly fewer escape failures es in the subsequent conditioned avoidance rest than those injected with control vector (HSV-LacZ). In contrast, microinjection of HSV-CREB in either the CAI pyramidal cell layer of hippocampus or the prefrontal cortex did, Eor produce antidepressant response, In the forced swim test CREB expression in the dentate gyrus resulted in a significantly shorter immobility time than those injected,with HSV-LacZConclusions: These results demonstrate that over-expression of CREB in hippocampus results in an antidepressant effect and suggest that CREB may sen e as a potential molecular target for novel therapeutic agents. (C) 2001 Society of Biological Psychiatry.