Pituitary adenylate cyclase activating peptide (PACAP) affects homeostatic sleep regulation in healthy young men

Pituitary adenylate cyclase activating peptide (PACAP) is involved in autonomous regulation by its action on the suprachiasmatic nucleus (SCN) and on neuroendocrine secretion. In rats PACAP promotes REM sleep. We investigated the effect of PACAP on human sleep. 4×12.5µg PACAP-38 or placebo were given hourly between 2200 and 0100 to young normal males. Sleep EEG was recorded from 2300 to 1000. Blood samples were collected simultaneously for the determination of ACTH, cortisol, growth hormone and prolactin. EEG spectral analysis revealed a significant reduction in the theta-frequency range in the first 4 hour interval of NonREM sleep and of the lower spindle frequency range in the second 4 hour interval of the registration period. This was accompanied by a reduction of the physiological delta-power decline during the night, i.e. an increase in the related time constant T from 339±75min after placebo to 558±326min after PACAP (p<0.05). As with SWS there is a reduced delta power accumulation in the early part of the registration period, whereas in the later intervals the cumulative SWS runs in parallel after PACAP and after placebo pointing to a reduced SWS need after PACAP administration. Furthermore a trend to a decreased prolactin secretion in the first 4 hour period of the night was found. No other endocrine changes were observed. In conclusion PACAP leads to a reduction of the dynamic of homeostatic sleep regulation and prolactin secretion.