大鼠冲动性的多巴胺能和 GABA 能标志物:腹侧纹状体和前额叶皮层的解剖定位证据。

Dopaminergic and GABA-ergic markers of impulsivity in rats: evidence for anatomical localisation in ventral striatum and prefrontal cortex.

机构信息

Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.

出版信息

Eur J Neurosci. 2013 May;37(9):1519-28. doi: 10.1111/ejn.12146. Epub 2013 Feb 1.

Abstract

Accumulating evidence indicates that impulsivity, in its multiple forms, involves cortical and subcortical mechanisms and abnormal dopamine (DA) transmission. Although decreased DA D2/D3 receptor availability in the nucleus accumbens (NAcb) predicts trait-like impulsivity in rats it is unclear whether this neurochemical marker extends to both the NAcb core (NAcbC) and shell (NAcbS) and whether markers for other neurotransmitter systems implicated in impulsivity such as serotonin (5-HT), endogenous opioids and γ-amino-butyric acid (GABA) are likewise altered in impulsive rats. We therefore used autoradiography to investigate DA transporter (DAT), 5-HT transporter (5-HTT) and D1, D2/D3, μ-opioid and GABA(A) receptor binding in selected regions of the prefrontal cortex and striatum in rats expressing low and high impulsive behaviour on the five-choice serial reaction-time task. High-impulsive (HI) rats exhibited significantly lower binding for DAT and D2/D3 receptors in the NAcbS and for D1 receptors in the NAcbC compared with low-impulsive (LI) rats. HI rats also showed significantly lower GABA(A) receptor binding in the anterior cingulate cortex. For all regions where receptor binding was altered in HI rats, binding was inversely correlated with impulsive responding on task. There were no significant differences in binding for 5-HTT or μ-opioid receptors in any of the regions investigated. These results indicate that altered D2/D3 receptor binding is localised to the NAcbS of trait-like impulsive rats and is accompanied by reduced binding for DAT. Alterations in binding for D1 receptors in the NAcbC and GABA(A) receptors in the anterior cingulate cortex demonstrate additional markers and putative mechanisms underlying the expression of behavioural impulsivity.

摘要

越来越多的证据表明,冲动以多种形式涉及皮质和皮质下机制以及异常的多巴胺(DA)传递。尽管伏隔核(NAcb)中减少的 DA D2/D3 受体可用性可预测大鼠的特质性冲动,但尚不清楚这种神经化学标志物是否扩展到 NAcb 核心(NAcbC)和壳(NAcbS),以及冲动性大鼠中涉及其他神经递质系统的标记物,如 5-羟色胺(5-HT)、内源性阿片样物质和 γ-氨基丁酸(GABA)是否也发生改变。因此,我们使用放射性自显影术研究了在表达低和高冲动行为的大鼠的前额叶皮层和纹状体的选定区域中 DA 转运蛋白(DAT)、5-HT 转运蛋白(5-HTT)和 D1、D2/D3、μ-阿片和 GABA(A)受体结合。与低冲动(LI)大鼠相比,高冲动(HI)大鼠在 NAcbS 中的 DAT 和 D2/D3 受体以及 NAcbC 中的 D1 受体的结合明显更低。HI 大鼠在前扣带皮层中的 GABA(A)受体结合也明显降低。在 HI 大鼠中改变结合的所有区域中,结合与任务中的冲动反应呈负相关。在任何研究的区域中,5-HTT 或 μ-阿片受体的结合均无显着差异。这些结果表明,改变的 D2/D3 受体结合定位于特质性冲动大鼠的 NAcbS,并且伴随着 DAT 结合减少。NAcbC 中的 D1 受体和前扣带皮层中的 GABA(A)受体的结合改变表明行为冲动表达的其他标记物和潜在机制。

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