Triazolam-induced sleep in the rat: influence of prior sleep, circadian time, and light/dark cycles.

Rats entrained to 12-h on /12-h off light schedule and injected with triazolam 0.4 mg/kg at the mid-point of their activity phase (6 h after lights out: circadian time = CT-18) had a stronger hypnotic response than animals free-running in constant dark injected at the equivalent circadian time. In contrast, entrained rats injected 5 h after lights on (CT-5) showed increased wake after injection relative to baseline, largely due to REM sleep inhibition. Hypnotic efficacy was found to be inversely related to prior accumulated sleep. During the 6 h before injection, entrained rats injected at CT-18 slept significantly less than the free-running rats, which in turn slept significantly less than entrained rats injected at CT-5. Taken together, the results suggest that the amount of prior sleep was a more important influence on the response to triazolam than either light/dark per se or circadian phase. Methodologically, automated sleep scoring was found to be an efficient method for examining drug effects, particularly when corroborated by concurrent independent physiological variables and spectral analysis.