Transient Hypoxia Alters Striatal Catecholamine Metabolism in Immature Brain: An In Vivo Microdialysis Study

Microdialysis probes were inserted bilaterally into the striatum of 7‐day‐old rat pups (n = 30) to examine extracellular fluid levels of dopamine, its metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5‐hydroxyindoleacetic acid (5‐HIAA). The dialysis samples were assayed by HPLC with electrochemical detection. Baseline levels, measured after a 2‐h stabilization period, were as follows: dopamine, not detected; DOPAC, 617 ± 33 fmol/min; HVA, 974 ± 42 fmol/min; and 5‐HIAA, 276 ± 15 fmol/min. After a 40‐min baseline sampling period, 12 animals were exposed to 8% oxygen for 120 min. Hypoxia produced marked reductions in the striatal extracellular fluid levels of both dopamine metabolites (p < 0.001 by analysis of variance) and a more gradual and less prominent reduction in 5‐HIAA levels (p < 0.02 by analysis of variance), compared with controls (n = 12) sampled in room air. In the first hour after hypoxia, DOPAC and HVA levels rose quickly, whereas 5‐HIAA levels remained suppressed. The magnitude of depolarization‐evoked release of dopamine (elicited by infusion of potassium or veratrine through the microdialysis probes for 20 min) was evaluated in control and hypoxic animals. Depolarization‐evoked dopamine efflux was considerably higher in hypoxic pups than in controls: hypoxic (n = 7), 257 ± 32 fmol/min; control (n = 12), 75 ± 14 fmol/min (p < 0.001 by analysis of variance). These data demonstrate that a brief exposure to moderate hypoxia markedly disrupts striatal catecholamine metabolism in the immature rodent brain.