Behavioral and EEG effects of 2-(7-chloro-l,8-naphthyridin-2-yl)-3-[(l,4)-dioxa-8-(azaspiro-[4.5]dec-8-yl)carbonylmethyl]isoindolin-l-one (DN-2327; 1, 5 and 20 mg/kg p.o.) were compared to those of diazepam (0.2 and 1 mg/kg p.o.) and buspirone (1 and 5 mg/kg p.o.) in freely moving cats. DN-2327 did not affect motor coordination or the relative percentages of the three sleep-wakefulness stages. Diazepam (1 mg/kg) increased wakefulness and non-REM sleep, and buspirone (5 mg/kg) also increased wakefulness and decreased REM sleep. In addition, diazepam (1 mg/kg) caused severe motor disturbance, but buspirone did not. The cortical EEG power density spectra during wakefulness were changed almost dose-dependently by DN-2327 (decreased: 2–7.75 Hz; increased: 20–49.75 Hz), and dose-dependently by diazepam (decreased: 2–7.75 Hz; increased 13–49.75 Hz) and buspirone (decreased: 4–9.75 and 13–19.75 Hz). The effect of DN-2327 on the cortical EEG varied with the sleep-wakefulness stage. The power of the 4- to 7.75-Hz frequency (theta) band of the hippocampal EEG during wakefulness was decreased by diazepam and buspirone but not by DN-2327, while the peak frequency of its spectra was decreased only by diazepam. On the other hand, during non-REM sleep, DN-2327 decreased the power of the theta band as did diazepam. These results indicate that the behavioral and EEG effects of DN-2327 differ completely from those of buspirone and considerably from those of diazepam and that the EEG effect of DN-2327 varies with the sleep-wakefulness stage.

Keywords:
Behavioral and EEG changes, Sleep-wakefulness stages, Power density spectrum, DN-2327, Diazepam, Buspirone, Cat
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© 1992 S. Karger AG, Basel
1992
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