Simultaneous activation of different subtypes of dopamine receptors may lead to activation of homeostatic sleep regulatory mechanisms.

Dopaminergic system gains importance in homeostatic sleep regulation, but the role of different dopamine receptors is not well-defined. 72 h rat electrocorticogram and sleep recordings were made after single application of dopaminergic drugs in clinical use or at least underwent clinical trials. The non-selective agonist apomorphine evoked short pharmacological sleep deprivation with intense wakefulness followed by pronounced sleep rebound. D2 agonist bromocriptine induced moderate and extended increase in wakefulness without a homeostatic sleep replacement but downregulated slow wave sleep need for 72 h. Selective D1 agonist SKF-38393 failed to induce enhanced waking sufficient for sleep replacement. High-dose D2 antagonism by sulpiride temporarily enhanced wakefulness. All drugs evoked extended (72 h) sleep changes after single application. Opposite sleep changes could be seen after the application of different doses in case of both bromocriptine and sulpiride. Theta, beta and gamma power reflected intensity differences in drug-induced wakefulness stages. Apomorphine- and high sulpiride dose-induced waking showed elevated power in all three frequency bands. Bromocriptine-induced wakefulness dominated by beta activity. Enhancement of more, than one type of electrocorticogram activities during wakefulness was a prerequisite for the activation of sleep homeostasis. According to present data, D1- or D2-like receptor agonism are not separately involved in the homeostatic regulation of slow wave sleep. Simultaneous and non-selective agonism on DA receptors is the most effective way to elicit intense W, which is followed by slow wave sleep rebound. REM sleep rebound could be evoked by D2 agonism. Rebound indicates the activation of homeostatic sleep regulation, but with unknown exact mechanisms.