The dopamine D1 receptor agonists, A68930 and SKF 38393, induce arousal and suppress REM sleep in the rat.
The effects of the dopamine D1 receptor full agonist, A68930, on sleep-wake patterns and grooming behaviour were studied in the rat. The partial dopamine D1 receptor agonist, SKF 38393, was used for comparison. A68930 (0.003-0.3 mg/kg s.c.) increased waking time, reduced the amount of rapid eye movement (REM) sleep and enhanced spontaneous grooming dose dependently. The ED50 were 0.06, 0.02 and 0.05 mg/kg, respectively. The D1 antagonist, SCH 23390 (0.003 mg/kg s.c.), blocked the effects of A68930 on wakefulness and grooming but not those on REM sleep. SKF 38393 (0.1-10 mg/kg s.c.) increased grooming with an ED50 of 1.4 mg/kg and a dose-response relationship similar to that of A68930 (potency ratio 28). Conversely, the increase of wakefulness and reduction of REM sleep caused by SKF 38393 had dose-response curves different from those of A68930. The results support the view that D1 receptors may have a physiological function in producing arousal.
Trampus
M
M
Research Laboratories, Schering-Plough S.p.A., Milan, Italy.
Ferri
N
N
Adami
M
M
Ongini
E
E
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D002839:Chromans; D015259:Dopamine Agents; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C065380:A 68930