SHORT- AND LONG-TERM EFFECTS OF PERINATAL ASPHYXIA ON MONOAMINE, AMINO-ACID AND GLYCOLYSIS PRODUCT LEVELS MEASURED IN THE BASAL GANGLIA OF THE RAT

The effects of perinatal asphyxia on levels of dopamine (DA) and its m etabolites, amino acids and glycolysis products, measured in tissue sa mples from substantia nigra(SN), striatum, ventral tegmental area (VTA ), and nucleus accumbens (Acb), were studied 80 min to 8 days after bi rth with high performance liquid chromatography (HPLC). Furthermore, e xtracellular levels of DA, amino acids and glycolysis products were me asured with in vivo microdialysis in the striatum 40-140 min and 4 wee ks after birth. Asphyxia was induced by immersing foetus-containing ut erus horns, removed from ready-to-deliver Sprague-Dawley rats, in a wa ter bath at 37 degrees C for various time periods (0-22 min). Spontane ous-and caesarean-delivered pups were used as controls. Perinatal asph yxia led to a decrease in the rate of survival, depending upon the len gth of the insult. In parallel, lactate (LACT) levels were increased w ith the length of the insult in all examined brain regions, monitored ex vivo or in vivo immediately after birth, DA, glutamate (GLU) and as partate (ASP) levels were also increased, mainly in tissue samples tak en from the mesencephalon. Only minor changes were observed in tissue samples taken from the telencephalon. However, in experiments with in vivo microdialysis, DA and GLU levels were increased following 20-21 a nd 21-22 min of perinatal asphyxia, but the effect of K+ depolarisatio n on extracellular DA and ASP levels was strongly diminished. DA and m etabolites increased with development in SN and striatum, with no clea r differences between control and asphyctic rats. However, 8 days afte r birth, it was found that DA levels were increased, alternatively dec reased in mesencephalic and telencephalic regions following 20-21 and 21-22 min of perinatal asphyxia, periods associated with 60% and 90% o f perinatal mortality, respectively. Furthermore, in microdialysis exp eriments performed 4 weeks after birth, extracellular DA and its metab olites levels were also increased, alternatively decreased in rats exp osed to a 20-21 and 21-22 min perinatal asphyctic insult. In this last group, GLU and ASP levels were also decreased. Furthermore, the effec t of K+ depolarisation on DA and ASP levels was strongly decreased in both asphyctic groups. Thus, perinatal asphyxia produces short-and lon g-term consequences in general metabolism, and induces region-specific changes in several neurotransmitter systems, mainly affecting meso-te lencephalic DA systems. (C) 1997 Elsevier Science B.V.