Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals

The circadian pacemaker in the suprachiasmatic nuclei is primarily synchron ized to the daily light-dark cycle. The phase-shifting and synchronizing ef fects of light can be modulated by non-photic factors, such as behavioral, metabolic or serotonergic cues. The present experiments examine the effects of sleep deprivation on the response of the circadian pacemaker to light a nd test the possible involvement of serotonergic and/or metabolic cues in m ediating the effects of sleep deprivation. Photic phase-shifting of the loc omotor activity rhythm was analyzed in mice transferred from a light-dark c ycle to constant darkness, and sleep-deprived for 8 h from Zeitgeber Time 6 to Zeitgeber Time 14. Phase-delays in response to a 10-min light pulse at Zeitgeber Time 14 were reduced by 30% in sleep-deprived mice compared to co ntrol mice, while sleep deprivation without light exposure induced no signi ficant phase-shifts. Stimulation of serotonin neurotransmission by fluoxeti ne (10 mg/kg), a serotonin reuptake inhibitor that decreases light-induced phase-delays in non-deprived mice, did not further reduce light-induced pha se-delays in sleep-deprived mice. Impairment of serotonin neurotransmission with p-chloroamphetamine (three injections of 10 mg/kg), which did not inc rease light-induced phase-delays in non-deprived mice significantly, partia lly normalized light-induced phase-delays in sleep-deprived mice. Injection s of glucose increased light-induced phase-delays in control and sleep-depr ived mice. Chemical damage of the ventromedial. hypothalamus by gold-thiogl ucose (600 mg/kg) prevented the reduction of light-induced phase-delays in sleep-deprived mice, without altering phase-delays in control mice. Taken t ogether, the present results indicate that sleep deprivation can reduce the light-induced phase-shifts of the mouse suprachiasmatic pacemaker, due to serotonergic and metabolic changes associated with the loss of sleep. (C) 2 001 Elsevier Science B.V. All rights reserved.