Mortality and ventilatory effects of central serotonin deficiency during postnatal development depend on age but not sex

Serotonin (5‐HT) influences brain development and has predominantly excitatory neuromodulatory effects on the neural respiratory control circuitry. Infants that succumb to sudden infant death syndrome (SIDS) have reduced brainstem 5‐HT levels and Tryptophan hydroxylase 2 (Tph2). Furthermore, there are age‐ and sex‐dependent risk factors associated with SIDS. Here we utilized our established Dark Agouti transgenic rat lacking central serotonin KO to test the hypotheses that CNS 5‐HT deficiency leads to: (1) high mortality in a sex‐independent manner, (2) age‐dependent alterations in other CNS aminergic systems, and (3) age‐dependent impairment of chemoreflexes during post‐natal development. KO rat pups showed high neonatal mortality but not in a sex‐dependent manner and did not show altered hypoxic or hypercapnic ventilatory chemoreflexes. However, KO rat pups had increased apnea‐related metrics during a specific developmental age (P12–16), which were preceded by transient increases in dopaminergic system activity (P7–8). These results support and extend the concept that 5‐HT per se is a critical factor in supporting respiratory control during post‐natal development.