Submitted on March 31, 2006
Accepted on October 31, 2006
Pituitary adenylyate cyclase activating peptide (PACAP) affects homeostatic sleep regulation in healthy young men
Harald Murck1, Axel Steiger1*, Ralf Michael Frieboes1, and Irina A. Antonijevic1
1 Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
* To whom correspondence should be addressed. E-mail: steiger{at}mpipsykl.mpg.de.
Pituitary adenylate cyclase activating peptide (PACAP) is involved in autonomous regulation including time keeping by action on the suprachiasmatic nucleus (SCN) 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 8 healthy male subjects. 4 x 12.5 µg PACAP was administered hourly between 22.00 and 01.00. Sleep EEG was recorded from 23.00 to 10.00.Blood samples were taken every 20 minutes between 22.00 and 07.00 for the determination of cortisol, growth hormone (GH) and prolactin. PACAP led to no changes in the macro-sleep structure. Spectral analysis revealed a significant reduction in the theta-frequency range in the first 4 hour interval and of the spindle frequency range in the second 4 hour interval of the registration period. This was accompanied with an increase in the time-constant 
of the physiological delta-power decline in the course of the night, i.e. less pronounced dynamics of the reduction of delta power with time. This was accompanied by a by trend (p < 0.1) decreased prolactin secretion in the first 4 hour period of the night. No other endocrine changes were observed. Conclusion: PACAP leads to a reduction of the dynamics of homeostatic sleep regulation and prolactin secretion. Both effects are opposite to those seen after sleep-deprivation but similar to the changes after napping, i.e. a reduced sleep propensity. PACAP might be involved in homeostatic sleep regulation.
