Department of Biology & Biochemistry, University of Bath, Bath, BA2 7AY, UK.
J Mol Neurosci. 2010 Jan;40(1-2):172-6. doi: 10.1007/s12031-009-9232-5. Epub 2009 Aug 18.
The aim of this study was to explore the modulation by alpha7 nicotinic receptors (nAChRs) of dopamine and glutamate release in the rat prefrontal cortex where these receptors are implicated in attentional processes and are therapeutic targets for cognitive deficits. The presence of presynaptic alpha7 nAChRs on glutamate terminals is supported by the ability of the subtype-selective agonist Compound A to evoke [(3)H]D-aspartate release from synaptosomes: This response was potentiated by the selective allosteric potentiator PNU-120596 and blocked by alphabungarotoxin. Compound A also evoked dopamine overflow in the prefrontal cortex in vivo, and this was potentiated by PNU-120596. alpha7 nAChR-evoked [(3)H]dopamine release from tissue prisms in vitro was blocked by antagonists of NMDA and AMPA receptors. These data are consistent with a model in which alpha7 nAChRs present on glutamate terminals increase glutamate release that (1) contributes to presynaptic facilitation and synaptic plasticity and (2) co-ordinately enhances dopamine release from neighbouring boutons.
本研究旨在探讨α7 型烟碱型乙酰胆碱受体 (nAChRs) 对大鼠前额叶皮层多巴胺和谷氨酸释放的调制作用，这些受体参与注意力过程，是认知缺陷的治疗靶点。谷氨酸末梢上存在突触前 α7 nAChR，这一观点得到以下事实的支持：亚型选择性激动剂化合物 A 能够诱发突触小体中 [(3)H]D-天冬氨酸的释放；这种反应被选择性变构调节剂 PNU-120596 增强，并被 α-银环蛇毒素阻断。化合物 A 也能在体内诱发前额叶皮层中的多巴胺溢出，而 PNU-120596 则增强了这种溢出。体外组织棱镜中 α7 nAChR 诱发的 [(3)H]多巴胺释放被 NMDA 和 AMPA 受体拮抗剂所阻断。这些数据与一种模型一致，即谷氨酸末梢上的 α7 nAChR 增加谷氨酸释放，(1) 有助于突触前易化和突触可塑性，(2) 协调增强来自邻近末梢的多巴胺释放。
