Effects of D-2 Antagonists on Frequency-Dependent Stimulated Dopamine Overflow in Nucleus Accumbens and Caudate-Putamen

Stimulated dopamine overflow has been measured with in vivo voltammetry in the caudate-putamen and nucleus accumbens. Overflow was induced by electrical stimulation of the medial forebrain bundle with 120 1-ms, 300-microA, biphasic pulses at frequencies between 10 and 60 Hz. Overflow was measured with a Nafion-coated, carbon-fiber electrode used with fast-scan voltammetry (300 V s-1). Quantification and identification of dopamine concentrations down to 100 nM in vivo is possible with this technique. The overflow curves were fit to a kinetic model that describes the measured response as a function of uptake (characterized by a Vmax and Km) and release (characterized by the concentration of dopamine released per stimulus pulse). Overflow curves in both regions could be described with similar kinetic parameters except for the Vmax, which in the nucleus accumbens was only 60% of that measured in the caudate-putamen. Uptake inhibition by nomifensine (20 mg kg-1) caused an apparent 15-fold change in the value of Km in the nucleus accumbens, similar to results previously reported in the caudate-putamen. In contrast, metoclopramide (10 mg kg-1) and sulpiride (100 mg kg-1) altered the apparent amount of dopamine released per stimulus pulse without a change in the uptake kinetics.