Behavioral and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
J Neurosci. 2011 May 18;31(20):7349-56. doi: 10.1523/JNEUROSCI.6182-10.2011.
Dopamine and dopamine-receptor function are often implicated in behavioral inhibition, and deficiencies within behavioral inhibition processes linked to attention deficit/hyperactivity disorder (ADHD), schizophrenia, obsessive-compulsive disorder, and drug addiction. In the stop-signal task, which measures the speed of the process of inhibition [stop-signal reaction time (SSRT)], psychostimulant-related improvement of SSRT in ADHD is linked with dopamine function. However, the precise nature of dopaminergic control over SSRT remains unclear. This study examined region- and receptor-specific modulation of SSRT in the rat using direct infusions of the dopamine D1 receptor (DRD1) antagonist SCH 23390 or dopamine D2 receptor (DRD2) antagonist sulpiride into the dorsomedial striatum (DMStr) or nucleus accumbens core (NAcbC). DRD1 and DRD2 antagonists had contrasting effects on SSRT that were specific to the DMStr. SCH 23390 decreased SSRT with little effect on the go response. Conversely, sulpiride increased SSRT but also increased go-trial reaction time and reduced trial completion at the highest doses. These results suggest that DRD1 and DRD2 function within the DMStr, but not the NAcbC, may act to balance behavioral inhibition in a manner that is independent of behavioral activation.
多巴胺和多巴胺受体功能通常与行为抑制有关,而与注意缺陷多动障碍(ADHD)、精神分裂症、强迫症和药物成瘾相关的行为抑制过程中的缺陷。在停止信号任务中,测量抑制过程的速度[停止信号反应时间(SSRT)],ADHD 中与精神兴奋剂相关的 SSRT 改善与多巴胺功能有关。然而,多巴胺对 SSRT 的精确控制性质尚不清楚。本研究使用多巴胺 D1 受体(DRD1)拮抗剂 SCH 23390 或多巴胺 D2 受体(DRD2)拮抗剂硫必利直接输注到背内侧纹状体(DMStr)或伏隔核核心(NAcbC),检查了大鼠 SSRT 的区域和受体特异性调制。DRD1 和 DRD2 拮抗剂对 SSRT 具有相反的影响,这对 DMStr 是特异性的。SCH 23390 降低了 SSRT,但对 Go 反应影响不大。相反,硫必利增加了 SSRT,但也增加了 Go 试验反应时间,并在最高剂量下减少了试验完成。这些结果表明,DRD1 和 DRD2 在 DMStr 中的功能,而不是在 NAcbC 中,可能以一种独立于行为激活的方式平衡行为抑制。