Differential effects of dopamine D-1 and D-2 receptor antagonist antipsychotics on sleep-wake patterns in the rat.
A series of antipsychotics having different selectivity for dopamine (DA) D-1 and D-2 receptors were studied for their effects on sleep stages in the rat. Electroencephalographic activity was recorded and classified according to the stages of wakefulness, rapid eye movement (REM) sleep and non-REM sleep. Total sleep duration, non-REM and REM latencies, number and duration of REM episodes were calculated. The DA D-1 antagonists, SCH 23390 (0.001-0.1 mg/kg s.c.), SCH 39166 (0.01-0.3 mg/kg s.c.) and NNC-756 (0.003-0.1 mg/kg s.c.), enhanced markedly the time spent in sleep through a significant increase of both non-REM and REM. Enhancement of REM was due to an increase in the number of episodes. The selective DA D-2 antagonists, raclopride (0.03-1 mg/kg s.c.) and remoxipride (1-10 mg/kg s.c.), did not affect sleep stages. Haloperidol (0.1-3 mg/kg p.o.) increased the duration of total sleep through an increase of non-REM, leaving REM unmodified. The nonselective DA antagonists, chlorpromazine (0.3-3 mg/kg s.c.) and clozapine (0.3-3 mg/kg s.c.) produced either no effect or slightly increased non-REM, respectively. Both drugs reduced REM duration by lowering the number and duration of episodes. The data show that there are differences between DA D-1 and D-2 antagonists with regard to their effects on sleep and wakefulness. Concomitant enhancement of both total sleep and REM appears to be a peculiar feature which clearly distinguishes DA D-1 antagonists from the other DA receptor blockers.(ABSTRACT TRUNCATED AT 250 WORDS)
Ongini
E
E
Research Laboratories, Schering-Plough S.p.A., Comazzo, Milan, Italy.
Bonizzoni
E
E
Ferri
N
N
Milani
S
S
Trampus
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D006220:Haloperidol