Guan X, Zhang R, Xu Y, Li S
Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Neuroscience. 2009 Jul 7;161(3):665-70. doi: 10.1016/j.neuroscience.2009.04.035. Epub 2009 Apr 17.
The neural plasticity mechanisms that underlie learning and memory may also be engaged when drug addiction occurs. It was reported that long-lasting neuroadaptations induced by cocaine use and withdrawal require the participation of hippocampus. However, the role of corticotrophin-releasing factor receptors in this process remains unclear. In the present study, the effects of chronic cocaine treatment (a 14-day cocaine administration, 20 mg/kg i.p., daily) and short-term cocaine withdrawal (a 3-day cocaine extinction following a 14-day cocaine administration) on long-term potentiation (LTP), one prominent cellular mechanism for learning and memory, were assessed in the CA1 region of the rat hippocampal slices. We found that cocaine withdrawal, but not the chronic cocaine administration itself, significantly enhanced the magnitude of LTP in hippocampal slices, as compared with that in saline controls. Selective blockade of corticotrophin-releasing factor receptor subtype 1 (CRF(1)) with the specific antagonist NBI 27914 (100 nM in vitro) attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats, and intriguingly, also from saline control rats, while specific blockade of corticotrophin-releasing factor receptor subtype 2 (CRF(2)) with astressin2-B (100 nM in vitro) selectively attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats. Our data suggest that short-term cocaine withdrawal treatment may cause synaptic plasticity in hippocampus partially via changing the activity of CRF(2) in the hippocampus.
药物成瘾发生时，学习和记忆所依赖的神经可塑性机制可能也会被激活。据报道，可卡因使用和戒断所诱导的持久神经适应性变化需要海马体的参与。然而，促肾上腺皮质激素释放因子受体在此过程中的作用仍不清楚。在本研究中，我们评估了慢性可卡因处理（连续14天腹腔注射可卡因，剂量为20mg/kg/天）和短期可卡因戒断（在连续14天给予可卡因后，进行3天的可卡因戒断）对长时程增强（LTP）的影响，LTP是学习和记忆的一种重要细胞机制，实验在大鼠海马脑片的CA1区进行。我们发现，与生理盐水对照组相比，可卡因戒断而非慢性可卡因处理本身，显著增强了海马脑片中LTP的幅度。用特异性拮抗剂NBI 27914（体外浓度为100nM）选择性阻断促肾上腺皮质激素释放因子受体1型（CRF(1)），可减弱可卡因戒断大鼠海马脑片中LTP的幅度，有趣的是，对生理盐水对照组大鼠海马脑片中LTP的幅度也有减弱作用；而用astressin2-B（体外浓度为100nM）特异性阻断促肾上腺皮质激素释放因子受体2型（CRF(2)），则选择性减弱了可卡因戒断大鼠海马脑片中LTP的幅度。我们的数据表明，短期可卡因戒断处理可能部分通过改变海马体中CRF(2)的活性而导致海马体的突触可塑性。
