Genetic depletion of 5HT increases central apnea frequency and duration and dampens arousal but does not impact the circadian modulation of these variables.

PURPOSE: We examined the impact of serotonin (5HT) on the frequency and duration of central apneic events, and the frequency of accompanying arousals, during non-rapid and rapid eye movement (NREM and REM) sleep across the light-dark cycle.

METHODS: Electroencephalography, electromyography, core body temperature and activity were recorded for 24 hours following implantation of telemeters in wild type (Tph2+/+ ) and tryptophan hydroxylase 2 knockout (Tph2-/- ) male mice.

RESULTS: (i) The frequency and duration of central apneic events was increased, (ii) the number of apneic events coupled to an arousal was decreased and (iii) the ventilatory sensitivity to hypoxia and hypercapnia was decreased in the Tph2-/- compared to the Tph2+/+ mice during NREM sleep. Apnea frequency and duration was similar in the Tph2-/- and Tph2+/+ mice during REM sleep. The duration of apneic events during REM compared to NREM sleep was similar in the Tph2-/- mice. In contrast, the duration was greater during REM sleep in the Tph2+/+ mice. Our results also revealed that apnea frequency was greater during the light compared to the dark cycle. Circadian modulation of this variable was evident in both the Tph2-/- and Tph2+/+ mice during NREM and REM sleep.

CONCLUSIONS: We conclude that depletion of 5HT increases the frequency and duration of central apneic events, dampens arousal and blunts the ventilatory response to hypoxia and hypercapnia during NREM sleep but is not essential for the circadian modulation of these variables.