Abstract

Intracerebral microdialysis was used to sample neurotransmitters from the extracellular fluid of the nucleus accumbens (NAS). Sample concentrations of dopamine and glutamate were assayed using high performance liquid chromatography followed by electrochemical detection. Sample glutamate concentrations decreased and then increased during the first ten to twelve hours following probe implantation. After stabilization sample glutamate and dopamine concentrations were estimated at a range of flow rates (0.25 $\mu$l/m, 0.5 $\mu$l/m, 1.0 $\mu$l/m, 2.0 $\mu$l/m); dopamine and glutamate concentrations varied inversely with the rate of perfusion. Estimates of the normal NAS extracellular glutamate and dopamine concentrations could not be obtained from these data using the "extrapolation to zero flow" method because there was no evidence of asymptotic yield within the range of flow rates that could be tested. An estimate of the normal NAS extracellular glutamate concentration (4.0 $\pm$ 0.8) was obtained using the no-net-flux method. The no-net-flux estimate was not significantly affected by an increase in the local depletion of dopamine and other small molecules caused by doubling the perfusate flow rate. The estimated extracellular glutamate concentration was 3.8 $\pm$ 0.8 $\mu$M at a flow rate of 0.5 $\mu$l/m and 4.25 $\pm$ 0.9 $\mu$M at a flow rate of 1.0 $\mu$l/min. These concentrations are not significantly different, suggesting that this increase in local depletion did not influence the activity of glutamate releasing cells in the tissue adjacent to the probe. Changes in dialysis sample dopamine concentration were determined during the extraction of NAS glutamate or the delivery of glutamate to the NAS. No significant changes in the sample dopamine concentration were associated with the perfusion of a range of glutamate concentrations surrounding the estimated NAS extracellular glutamate concentration.