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.
Monti
J M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay.
Jantos
H
H
Fernández
M
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004569:Electroencephalography; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D014150:Antipsychotic Agents; D001549:Benzamides; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C030265:nemonapride