Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake

Advances in measurement techniques have enabled the extracellular concentration of dopamine to be monitored inside striatal structures during transient electrical stimulation of the medial forebrain bundle. The observed concentration changes can be accounted for by a mathematical model as a function of the frequency employed and the stimulus duration. Overflow curves can be described by 3 kinetic parameters: the concentration of dopamine released per stimulus pulse, and the Km and Vmax of uptake. In terms of this model, the kinetics of overflow during stimulation is found to be identical in the nucleus accumbens and caudate nucleus with the exception that the Vmax for uptake is lower in the former region. Maximal uptake is also found to be lower in animals with partial lesions of dopamine neurons. Measured concentrations vary with stimulation frequency from 10 to 60 Hz in a manner that can be predicted by the model. Competitive uptake inhibitors have their primary effect on overflow in the limit of low stimulus frequencies. In contrast, D2 antagonists, which increase the concentration of dopamine released per stimulus pulse, have a moderate effect in low and high frequency ranges, but cause a significant maximal increase in extracellular dopamine concentrations at a mid-range frequency. Both calculated response and experimental findings indicate that in the caudate nucleus, the upper frequency for observable uptake inhibition and the characteristic maximum frequency for the receptor-mediated response occur at higher values than in the nucleus accumbens. The model appears to be useful for predicting dopamine extracellular concentrations over a wide range of conditions, and its predictions may be valid when extended to more physiological situations.