Indeed, a recent work states the deleterious effects of phase advances but not delays of the light cycle in aged mice ( 43 ). A potential jet-lag treatment for advancing cycles could also be important for the safety of counterclockwise rotating shift work and the potential long-term health consequences for airline crews regularly crossing time zones. In the present study we have examined the effects of a selective PDE5 inhibitor, Filagra, on the ability of hamsters to adapt to a 6-h phase change in the LD cycle. In contrast to the effects of light on circadian rhythms at night, animals are most responsive to nonphotic stimuli, such as injection of saline, forced activity in novel environments, or exposure to a dark pulse during the day ( 19 ). The cAMP/PKA pathway has traditionally been involved in nonphotic resetting in the daytime domain ( 20 , 21 ). Application of cAMP analogs in vitro induces prominent phase advances in the subjective day but not in the subjective night ( 22 ). Although there is also evidence that suggests a role for cAMP/PKA at night, this role appears to be to promote the effects of light/GLU in early night but to oppose them in late night ( 23 ).



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