METABOLIC RESPONSES OF THE DOPAMINERGIC SYSTEM DURING HYPOXIA IN NEWBORN BRAIN

The purpose of this review is to describe the relationship between the dopamine and amino acid neurotransmitter systems and cortical oxygen pressure during different levels of cerebral hypoxia using newborn pig lets as an animal model, adding new data from our laboratory. The extr acellular dopamine increases as the oxygen pressure in the cortex decr eases. The relationship between oxygen pressure and dopamine levels is the same whether the hypoxia is induced by reduced FiO2 (high-how hyp oxia) or by hypocapnia-induced cerebral vasoconstriction (Low-flow hyp oxia). Thus it appears that, particularly in mild hypoxia, the extrace llular level of dopamine depends primarily on the oxygen concentration in the tissue with minimal influence of parameters such as blood flow and pH. There is no ''oxygen reserve'' in the brain of newborn piglet s and the extracellular levels of dopamine in the striatum increase al most linearly with decrease in oxygen pressure, with even small decrea ses in oxygen pressure resulting in increased dopamine levels. In cont rast, the changes in extracellular concentrations of the excitatory am ino acids glutamate and aspartate are variable and transient. In a maj ority of 2- to 5 day-old piglets even very low oxygen pressures in the brain did not result in significant alterations in the extracellular levels of glutamate and aspartate. These changes in the dopaminergic s ystem may contribute directly and indirectly to the neuronal damage th at occurs during hypoxic/ischemic insult and reoxygenation in newborn brain, particularly in the striatum. A variety of mechanisms are discu ssed by which dopamine, in particular extracellular dopamine, can incr ease cellular toxicity.