Figure 2.

Effects of Nicotinic acetylcholine receptor α₄ on rat sleep architecture (associated traits: Wake, Total Sleep, non-REM). Average time spent per 30-minute interval in active wake, light sleep, SWS sleep, and REM sleep in response to vehicle treatment (closed circles) versus treatment with (A) varenicline and (B) cytisine (open circles). Dark bars in x -axis represent lights-off period, with time of dosing indicated with an arrowhead on each graph. Values are mean ± SEM (short, medium, and long tic marks represent p ≤ .05, ≤ .01, ≤ .001; linear mixed effects model for repeated measures). Average percent changes in sleep stage (C) cumulative time and (D) bout durations (mean time in sleep stage divided by bout number) following treatment of rats with varenicline (closed bars) and cytisine (open bars) for active phase (from time of dosing to ZT 00:30) and inactive phase (ZT 00:30-2:30). Sleep stages are indicated as follows: active wake (AW), light sleep (LS), slow wave sleep (SWS), and REM sleep (REM). Plotted values represent percent difference from vehicle within independent experiments for each dose, and calculated from raw sleep stage time and bout data. Plotted values are mean ±SEM (• p ≤.05, •• p ≤.01, ••• p ≤.001; two-tailed population t test). Each study run as a balanced crossover design, with 7 sequential days of dosing for varenicline treatment (n=8 animals, 56 nights/condition total, 1 mg/kg, p.o., dosed ZT 23:30) and for cytisine treatment (n=8 animals, 56 nights/condition total, 1.5 mg/kg, i.p., dosed ZT 23:00).