Constant light housing during nursing causes human DSPS (delayed sleep phase syndrome) behaviour in Clock-mutant mice

Delayed sleep phase syndrome (DSPS) is very often seen among patients with sleep-wake rhythm disorders. Humans with the 3111C allele of the human Clock gene tend to demonstrate a higher evening preference on the morningness-eveningness (ME) preference test. DSPS is thought to be an extreme form of this evening preference. Clock-mutant mice have been proposed as an animal model of evening preference. In this study, we looked at whether constant light (LL) housing of Clock-mutant mice during lactation would result in evening preference and/or DSPS. Housed under light-dark (LD) or constant dark (DD) conditions during the lactation period, both wild-type and Clock-mutant mice did not show a phase-delay in the locomotor activity measured under light-dark conditions, whereas constant light housing during lactation significantly caused a delayed onset. The magnitude of the delay during the light-dark cycle was positively associated with free-running period measured during constant darkness. Among wild, heterozygote, and homozygote pups born from heterozygous dams, only homozygote pups showed a delayed onset. Constant light-housed Clock-mutant mice exhibited a lower number and delayed peak of phospho-MAPK-immunoreactive cells in core regions of the suprachiasmatic nucleus (SCN) compared to light-dark housed wild-type or Clock-mutant mice. Activity onset returned to normal with daily melatonin injection at the lights-off time for 5 days. The present results demonstrate that Clock-mutant mice exposed to constant light during lactation can function as an animal model of DSPS and can be used to gain an understanding of the ethological aspects of DSPS as well as to find medication for its treatment.