ANOMALOUSLY HIGH-CONCENTRATIONS OF BRAIN EXTRACELLULAR URIC-ACID DETECTED WITH CHRONICALLY IMPLANTED PROBES - IMPLICATIONS FOR INVIVO SAMPLING TECHNIQUES

The height of peak 2, h2, recorded using linear sweep voltammetry with 350-mu-m-diameter carbon paste electrodes in rat striatum was measured from the day of implantation (day 0) to 4 months after surgery. The value of h2 was at a minimum on day 0 (0.6 +/- 0.2 nA; n = 20), rose sharply to a maximum on day 2 (6.3 +/- 0.9 nA; n = 12), and decreased to a stable level by day 7 (3.3 +/- 0.7 nA; n = 16), which lasted for 4 months (3.2 +/- 0.6 nA; n = 9). These changes were shown by microinfusion of uricase to be due to variations in the concentration of extracellular uric acid, although h2 appears to have a small baseline contribution of approximately 0.3 nA from 5-hydroxyindoleacetic acid. The stable value of h2 recorded under chronic conditions was estimated to correspond to a minimal uric acid concentration of 50-mu-mol/L, which represents a 10-fold increase in the extracellular level of this purine metabolite compared with the initial (acute) value. Very similar results were obtained using a microdialysis technique that detected uric acid directly. These estimates of striatal uric acid concentration are in marked contrast to those obtained using 40-mu-m diameter carbon fiber electrodes, which showed a decrease from the acute preparation to < 1-mu-mol/L under chronic conditions. Large values of h2 were also recorded with chronically implanted paste electrodes in the hippocampus and frontal cortex. The results suggest that large in vivo probes, such as carbon paste electrodes and dialysis tubes, markedly disturb the neurochemical balance in the extracellular fluid even 1 day following implantation and emphasize the need to develop further small sensors for in vivo neurochemical analysis with minimal perturbation.