Flurazepam and triazolam: dose-response and time-response evaluation on cat sleep

A window discrimination method is presented for the continuous monitoring of sleep-wakefulness cycles in cats. Window discrimination permits the recording of the frequency of firing of multiple units, while filtering out movement artifacts and low-level noise. Records of reticular formation multiple unit activity (MUA) and EMG from cats with chronically implanted electrodes were quantified by window discrimination and displayed on a strip chart recorder. The frequency of firing of large reticular multiple units was highest in states of high CNS excitation (i.e., REM), and the lowest in states of low CNS excitation (i.e., SWS). Comparison of recording of reticular MUA by window discrimination and rectification-integration indicated that sleep-wakefulness states were more easily distinguished with the former method. The effects of flurazepam, 1.25-5 mg/kg i.p., and triazolam, 0.01-0.05 mg/kg i.p., on reticular MUA were observed for 24-72 h of continuous recording. Both benzodiazepines depressed reticular MUA by up to 50% in a dose-related fashion. Flurazepam was effective for 72 h or more, and triazolam for 24-48 h. Flurazepam was also much longer lasting than triazolam when administered for 3 days at 24 h intervals. As evidence by our evaluation of flurazepam and triazolam, it appears that evaluation of the effects of sedative-hypnotics on the CNS excitation level of the cat, and the duration of these effects, can be readily performed and these results generalized to the clinical experience. This should prove useful in the evaluation of novel sedative-hypnotics.