Isaac Stuart O, Berridge Craig W
Department of Psychology, University of Wisconsin, Madison, WI 53706, USA.
J Pharmacol Exp Ther. 2003 Oct;307(1):386-94. doi: 10.1124/jpet.103.053918. Epub 2003 Aug 27.
Multiple ascending neurotransmitter systems participate in the regulation of behavioral state. For example, noradrenergic, cholinergic, and serotonergic systems increase EEG and, in some cases, behavioral indices of arousal. The extent to which dopaminergic systems exert a similar activating influence on behavioral state remains unclear. The current studies examined the wake-promoting actions of centrally administered D1 and D2 receptor agonists. In these studies, intracerebroventricular infusions of a D1 (SKF-82958; 2.5 and 25 nmol) or D2 (quinpirole; 40 and 140 nmol)-agonist were made into sleeping animals. The effects of these infusions on electroencephalogram/electromyographic indices of sleep-wake state and behavior were examined. D1 agonist administration dose dependently increased time spent awake and suppressed rapid eye movement and slow-wave sleep in the 2 h immediately after infusion. D1 agonist administration also elicited modest increases in measures of locomotion and time spent grooming and eating. D2 agonist administration had similar wake-promoting actions, accompanied by modest effects on drinking and locomotion. Interestingly, D2 agonist administration also significantly increased time spent chewing on inedible material, an arousal/stress-related behavior. Overall, these results demonstrate that dopamine contributes to the alert waking state via actions of D1 and D2 receptors. Additionally or alternatively, these results further suggest a potential involvement of dopamine receptors in the induction of high-arousal states, including stress.
多种上行神经递质系统参与行为状态的调节。例如,去甲肾上腺素能、胆碱能和血清素能系统会增加脑电图,在某些情况下还会增加觉醒的行为指标。多巴胺能系统对行为状态产生类似激活影响的程度尚不清楚。目前的研究考察了中枢给予D1和D2受体激动剂促进觉醒的作用。在这些研究中,将D1(SKF-82958;2.5和25纳摩尔)或D2(喹吡罗;40和140纳摩尔)激动剂脑室内注入睡眠中的动物。考察了这些注入对睡眠-觉醒状态和行为的脑电图/肌电图指标的影响。注入D1激动剂后,在紧接着的2小时内,剂量依赖性地增加了清醒时间,并抑制了快速眼动睡眠和慢波睡眠。注入D1激动剂还适度增加了运动以及梳理毛发和进食时间的测量值。注入D2激动剂有类似的促进觉醒作用,同时对饮水和运动有适度影响。有趣的是,注入D2激动剂还显著增加了咀嚼不可食用材料的时间,这是一种与觉醒/应激相关的行为。总体而言,这些结果表明多巴胺通过D1和D2受体的作用有助于警觉的清醒状态。此外或作为另一种情况,这些结果进一步表明多巴胺受体可能参与包括应激在内的高觉醒状态的诱导。