Wake-promoting actions of dopamine D1 and D2 receptor stimulation

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.