Sildenafil accelerates reentrainment of circadian rhythms

AGOSTINO, PV; PLANO, SA; GOLOMBEK, DA

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2007 vol. 104 p. 9834 - 9839

0027-8424

Mammalian circadian rhythms are generated by a master clock located in the suprachiasmatic nuclei and entrained by light- activated signaling pathways. In hamsters, the mechanism respon- sible for light-induced phase advances involves the activation of guanylyl cyclase, cGMP and its related kinase (PKG). It is not completely known whether interference with this pathway affects entrainment of the clock, including adaptation to changing light schedules. Here we report that cGMP-specific phosphodiesterase 5 is present in the hamster suprachiasmatic nuclei, and administra- tion of the inhibitor sildenafil (3.5 mg/kg, i.p.) enhances circadian responses to light and decreases the amount of time necessary for reentrainment after phase advances of the light? dark cycle. These results suggest that sildenafil may be useful for treatment of circadian adaptation to environmental changes, including trans- meridian eastbound flight schedules.