Effects of the selective dopamine D-2 receptor agonist, quinpirole on sleep and wakefulness in the rat.

The effects of the dopamine D-2 receptor agonist, quinpirole, were compared with those produced by dopamine D-2 antagonist, YM-09151-2, in rats implanted with electrodes for chronic sleep recordings. Quinpirole (0.015-1.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness and increased sleep, while higher doses induced the opposite effects. At 0.015 mg/kg, YM-09151-2 slightly augmented wakefulness, while at 1.0-2.0 mg/kg it significantly increased light sleep but depressed REM sleep. Pretreatment with YM-09151-2 in a dose which preferentially acts at presynaptic sites reversed the suppressant effects of a low dose of quinpirole on wakefulness and slow wave sleep. In contrast, the administration of YM-09151-2 in a dose which blocks postsynaptic D-2 receptors prevented the effect of a high dose of quinpirole on wakefulness and slow wave sleep; the depression of REM sleep was not affected. The opposite effects observed on the waking EEG after activation of either dopamine autoreceptors or postsynaptic D-2 receptors with adequate doses of quinpirole tend to indicate an active role for DA in the control of the waking state.