The influence of stimulus parameters on the potentiation of striatal dopamine release by metoclopramide: in vivo voltammetric data.

Carbon fibre microelectrodes were implanted acutely into the striatum of chloral hydrate-anaesthetised rats to measure the dopamine released by electrical stimulation of the ipsilateral nigrostriatal pathway. High speed cyclic voltammetry was used throughout. The effects of metoclopramide and of different stimulation parameters (frequency and duration) were investigated. Using a 10 s stimulus train, it was found that frequencies less than 25 Hz evoked little measurable dopamine release. Maximum release occurred at 50-62.5 Hz. Metoclopramide (2.5-20 mg/kg i.p.) increased stimulated dopamine release in a dose-dependent fashion. The effect of metoclopramide (10 mg/kg) was investigated in detail at 25, 37.5 and 50 Hz stimulation frequency and at 2.5, 5.0 and 10.0 s after the onset of stimulation. Metoclopramide, at all stimulation frequencies, caused the largest percentage elevation of release at 2.5 s of stimulation. The results indicate that prolonged stimulation can deplete the releasable pool of dopamine and mask the effects of dopamine receptor blockade.