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获得一种欲求行为可防止大鼠伏隔核中应激诱导的神经化学修饰的发展。

Acquisition of an appetitive behavior prevents development of stress-induced neurochemical modifications in rat nucleus accumbens.

作者信息

Nanni Giulio, Scheggi Simona, Leggio Benedetta, Grappi Silvia, Masi Flavio, Rauggi Riccardo, De Montis Maria Graziella

机构信息

Department of Neuroscience, University of Siena, Siena, Italy.

出版信息

J Neurosci Res. 2003 Aug 15;73(4):573-80. doi: 10.1002/jnr.10685.

Abstract

In rats, exposure to chronic unavoidable stress produces a decrease in dopamine output in the nucleus accumbens shell that is accompanied by a decreased density of the dopamine transporter and an increased activity of the dopamine-D(1) receptor complex. These modifications have been hypothesized to be adaptive to decreased dopamine output in stressed rats. We investigated whether the learning of an appetitive behavior sustained by palatable food, which is associated with increased dopamine output in the nucleus accumbens shell as measured by microdialysis experiments, would affect the modifications induced by chronic stress exposure on dopamine transporter density and dopamine-D(1) receptor complex activity in the nucleus accumbens. Rats exposed to chronic unavoidable stress after acquisition of the appetitive behavior showed a higher dopamine extraneuronal release in the nucleus accumbens shell than that of stressed animals, and similar to that of control rats. Moreover, previous acquisition of the appetitive behavior prevented development of a stress-induced decrease in dopamine transporter density, measured by [(3)H]-WIN 35428 binding, a stress-induced increase in dopamine-D(1) receptor density, measured by binding of [(3)H]-SCH 23390, and SKF 38393-stimulated adenylyl cyclase activity in the nucleus accumbens. These results support the hypothesis that changes induced in pre- and postsynaptic dopaminergic transmission by chronic stress exposure are related to decreased dopamine output.

摘要

在大鼠中,长期暴露于不可避免的应激会导致伏隔核壳部多巴胺输出减少,同时伴有多巴胺转运体密度降低和多巴胺D(1)受体复合物活性增加。这些改变被认为是对应激大鼠多巴胺输出减少的适应性反应。我们研究了通过微透析实验测量,由美味食物维持的奖赏行为学习(这与伏隔核壳部多巴胺输出增加相关)是否会影响慢性应激暴露对伏隔核中多巴胺转运体密度和多巴胺D(1)受体复合物活性的诱导改变。在习得奖赏行为后暴露于慢性不可避免应激的大鼠,其伏隔核壳部的多巴胺细胞外释放高于应激动物,且与对照大鼠相似。此外,先前习得的奖赏行为可防止应激诱导的多巴胺转运体密度降低(通过[(3)H]-WIN 35428结合测量)、应激诱导的多巴胺D(1)受体密度增加(通过[(3)H]-SCH 23390结合测量)以及伏隔核中SKF 38393刺激的腺苷酸环化酶活性增加。这些结果支持了这样的假设,即慢性应激暴露在突触前和突触后多巴胺能传递中诱导的变化与多巴胺输出减少有关。

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