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Pituitary adenylate cyclase-activating peptide affects homeostatic sleep regulation in healthy young men

Max Planck Institute of Psychiatry, Munich, Germany

Submitted 31 March 2006 ; accepted in final form 31 October 2006

Pituitary adenylate cyclase-activating peptide (PACAP) is involved in autonomous regulation, including timekeeping, by its action on the suprachiasmatic nucleus and on neuroendocrine secretion, energy metabolism, and transmitter release. In particular, the interactions between PACAP and the glutamatergic system are well recognized. We compared the effect of intravenously administered PACAP to that of placebo in eight healthy male subjects. PACAP in a concentration of 4 x 12.5 µg was administered in a pulsatile fashion hourly between 2200 and 0100. Sleep EEG was recorded from 2300 to 1000, which was also the time when subjects were allowed to sleep. Blood samples were taken every 20 min between 2200 and 0700 for the determination of cortisol, GH, and prolactin. PACAP administration led to no changes in the macro-sleep structure as assessed according to standard criteria. Spectral analysis revealed a significant reduction in the -frequency range in the first 4-h interval and of the spindle frequency range in the second 4-h interval of the registration period. This was accompanied by an increase in the time constant of the physiological -power decline in the course of the night, i.e., a less pronounced dynamic of the reduction of -power with time. This was accompanied by a trend (P < 0.1) toward decreased prolactin secretion in the first 4-h period of the night. No other changes in endocrine secretion were observed. We concluded that PACAP leads to a reduction of the dynamics of homeostatic sleep regulation and prolactin secretion. Both effects are the opposite of those seen after sleep deprivation but similar to the changes after napping, i.e., a reduced sleep propensity. This implies that PACAP might be involved in homeostatic sleep regulation.

cortisol; growth hormone; prolactin