Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens.
Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens.
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DOI：
10.1523/jneurosci.4961-07.2008
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发表时间：
2008-07-09
影响因子：
5.3
通讯作者：
Berridge, Kent C.
中科院分区：
文献类型：
--
作者：
Faure, Alexis;Reynolds, Sheila M.;Richard, Jocelyn M.;Berridge, Kent C.
情感神经科学的一个重要问题涉及中皮质边缘多巴胺系统在正价动机（例如奖励）与负价动机（例如恐惧）中的作用。在这里，我们评估了伏隔核内源性多巴胺受体刺激是否有助于食欲行为和恐惧行为，这些行为是通过内侧壳不同部位的局部谷氨酸破坏而以键盘方式产生的。 6,7-二硝基喹喔啉-2,3(1H,4H)-二酮 (DNQX) 微量注射 (450 ng) 局部破坏 <4 mm3 伏隔核中的谷氨酸信号，并根据内壳中精确的轴尾位置产生欲望或恐惧（或两者）。在喙壳位点，局部 AMPA/红藻氨酸阻断产生积极的摄取行为，但随着相同的显微注射向尾部移动，引发的动机行为变得越来越令人恐惧。将 D1 和 D2 拮抗剂（雷氯必利和 SCH-23390 [R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5,-四氢-1H-3-苯并氮杂盐酸盐]）的多巴胺阻断混合物与 DNQX 组合在同一显微注射中，以评估内源性局部多巴胺在介导 DNQX 激发中的作用行为。我们报告说，局部多巴胺阻断阻止 DNQX 微注射在头壳中产生食欲行为（进食），并且同样阻止 DNQX 在尾壳中产生恐惧行为（防御性踩踏）。我们得出的结论是，需要局部多巴胺来破坏壳中的皮质边缘谷氨酸信号，以产生积极的激励显着性或消极的恐惧显着性（效价取决于地点和其他条件）。因此，多巴胺与内侧壳中偏价谷氨酸电路的定位相互作用，以促进食欲和恐惧动机的键盘刺激。
An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial shell. 6,7-Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm3 of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial shell. At rostral shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. A dopamine-blocking mixture of D1 and D2 antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride]) was combined here in the same microinjection with DNQX to assess the role of endogenous local dopamine in mediating the DNQX-motivated behaviors. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial shell to facilitate keyboard stimulation of both appetitive and fearful motivations.