Serotonin metabolism in neonatal rat brain during asphyxia and recovery.

Neonatal rats were exposed to 20 or 30 min of total or partial oxygen deprivation. During asphyxia and subsequent recovery the endogenous levels of tryptophan and 5-hydroxytryptamine (5-HT, serotonin) were measured. The activity of tryptophan hydroxylase, the first and rate limiting enzyme in the 5-HT synthesis pathway, was studied in vivo by measuring the accumulation of 5-hydroxytryptophan (5-HTP) after inhibition of aromatic L-amino acid decarboxylase with NSD 1015. During asphyxia there was a decrease in tryptophan hydroxylase activity in the whole brain and various regions studied. The levels of tryptophan, 5-HTP and 5-HT all increased after 30 min of recovery from asphyxia. In the whole brain, 5-HTP and 5-HT levels were normal 2 h after anoxia while tryptophan levels normalized more slowly to reach control values after 6 h. In the regional brain study, the 5-HTP levels returned quickly to control levels after asphyxia in the striatum and midbrain but not in the brainstem and hemispheres regions. The whole brain 5-HTP and 5-HT levels did not differ from controls 24 to 48 h after the asphyxia. Although the neonatal nervous system exhibits a great resistance to asphyxia, the metabolism of the neurotransmitter 5-HT is affected already during a short period of asphyxia and subsequent recovery. As 5-HT is ascribed important neurotransmitter functions, this might be relevant to the neurological sequelae of human asphyxia neonatorum.