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Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.多巴胺奖赏回路：从腹侧中脑到伏隔核 - 嗅结节复合体的两个投射系统。
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伏隔核中的腺苷酸环化酶-5活性调节与焦虑相关的行为。

Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior.

作者信息

Kim Kyoung-Shim, Lee Ko-Woon, Baek In-Sun, Lim Chae-Moon, Krishnan Vaishnav, Lee Ja-Kyeong, Nestler Eric J, Han Pyung-Lim

机构信息

Division of Nano Sciences and Brain Disease Research Institute, Ewha Womans University, Seoul, Korea.

出版信息

J Neurochem. 2008 Oct;107(1):105-15. doi: 10.1111/j.1471-4159.2008.05592.x. Epub 2008 Jul 31.

DOI:10.1111/j.1471-4159.2008.05592.x
PMID:18673448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2744302/
Abstract

Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal striatum and nucleus accumbens (NAc), two brain areas which have been implicated in motor function, reward, and emotion. Here we demonstrate that mice lacking AC5 (AC5-/-) display strong reductions in anxiety-like behavior in several paradigms. This anxiolytic behavior in AC5-/- mice was reduced by the D(1) receptor antagonist SCH23390 and enhanced by the D(1) dopamine receptor agonist, dihydrexidine (DHX). DHX-stimulated c-fos induction in AC5-/- mice was blunted in the dorso-lateral striatum, but it was overactivated in the dorso-medial striatum and NAc. The siRNA-mediated inhibition of AC5 levels within the NAc was sufficient to produce an anxiolytic-like response. Microarray and RT-PCR analyses revealed an up-regulation of prodynorphin and down-regulation of cholecystokinin (CCK) in the NAc of AC5-/- mice. Administration of nor-binaltorphimine (a kappa opioid receptor antagonist) or CCK-8s (a CCK receptor agonist) reversed the anxiolytic-like behavior exhibited by AC5-/- mutants. Taken together, these results suggest an essential role of AC5 in the NAc for maintaining normal levels of anxiety.

摘要

5型腺苷酸环化酶（AC5）高度集中于背侧纹状体和伏隔核（NAc），这两个脑区与运动功能、奖赏和情绪有关。在此我们证明，缺乏AC5的小鼠（AC5-/-）在多种实验范式中表现出焦虑样行为的显著减少。AC5-/-小鼠的这种抗焦虑行为被D(1)受体拮抗剂SCH23390减弱，并被D(1)多巴胺受体激动剂二氢麦角隐亭（DHX）增强。DHX刺激AC5-/-小鼠的c-fos诱导在背外侧纹状体中减弱，但在背内侧纹状体和伏隔核中过度激活。NAc内siRNA介导的AC5水平抑制足以产生抗焦虑样反应。微阵列和RT-PCR分析显示，AC5-/-小鼠的NAc中前强啡肽上调，胆囊收缩素（CCK）下调。给予去甲纳曲酮（一种κ阿片受体拮抗剂）或CCK-8s（一种CCK受体激动剂）可逆转AC5-/-突变体表现出的抗焦虑样行为。综上所述，这些结果表明AC5在NAc中对于维持正常焦虑水平起着至关重要的作用。