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首页> 外文期刊>Genes, brain, and behavior >Restructuring of basal ganglia circuitry and associated behaviors triggered by low striatal D2 receptor expression: implications for substance use disorders
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Restructuring of basal ganglia circuitry and associated behaviors triggered by low striatal D2 receptor expression: implications for substance use disorders

机译：低纹状体D2受体表达触发基底神经节电路的重组和相关行为：物质使用障碍的影响

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摘要

Dopamine D2 receptors (D2Rs) consistently emerge as a critical substrate for the etiology of some major psychiatric disorders. Indeed, a central theory of substance use disorders (SUDs) postulates that a reduction in D2R levels in the striatum is a determining factor that confers vulnerability to abuse substances. A large number of clinical and preclinical studies strongly support this link between SUDs and D2Rs; however, identifying the mechanism by which low D2Rs facilitate SUDs has been hindered by the complexity of circuit connectivity, the heterogeneity of D2R expression and the multifaceted constellation of phenotypes observed in SUD patient. Animal models are well-suited for understanding the mechanisms because they allow access to the circuitry and the genetic tools that enable a dissection of the D2R heterogeneity. This review discusses recent findings on the functional role of D2Rs and highlights the distinctive contributions of D2Rs expressed on specific neuronal subpopulations to the behavioral responses to stimulant drugs. A circuit-wide restructuring of local and long-range inhibitory connectivity within the basal ganglia is observed in response to manipulation of striatal D2R levels and is accompanied by multiple alterations in dopamine-dependent behaviors. Collectively, these new findings provide compelling evidence for a critical role of striatal D2Rs in shaping basal ganglia connectivity; even among neurons that do not express D2Rs. These findings from animal models have deep clinical implications for SUD patients with low levels D2R availability where a similar restructuring of basal ganglia circuitry is expected to take place.
机译：多巴胺D2受体（D2RS）一致地作为一些主要精神疾病的病因的关键基础。实际上，物质使用障碍（suds）的中央理论假定纹状体中的D2R水平降低是赋予滥用物质脆弱性的决定因素。大量临床和临床前研究强烈支持苏打和D2R之间的这种联系;然而，鉴定低D2Rs促进泡沫的机制已经受到电路连接的复杂性的阻碍，D2R表达的异质性和在抑菌患者中观察到的表型的多方型星座。动物模型非常适合理解机制，因为它们允许进入电路和能够解剖D2R异质性的遗传工具。该审查讨论了最近关于D2R的功能作用的发现，并突出了对特定神经细胞群表达的D2Rs对兴奋剂的行为反应的独特贡献。响应于纹状体D2R水平的操纵，观察到基底神经节内的局部和远程抑制连接内的局部和远程抑制连接的电路范围内重组，并伴随着多巴胺依赖性行为的多重改变。集体，这些新发现为纹状体D2RS在塑造基底神经节连通性方面的关键作用提供了令人信服的证据;甚至在不表达D2RS的神经元中。来自动物模型的这些发现对抑菌患者具有深入的D2R可用性患者，其中预期基部Ganglia电路的类似重组。

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