Regulation of dopamine release by impulse flow and by autoreceptors as studied by in vivo voltammetry in the rat striatum.

Extracellular dopamine concentration has been monitored in the striatum of pargyline treated, anaesthetized rats using differential normal pulse voltammetry. The catechol oxidation current recorded with electrochemically treated carbon fiber electrodes disappeared when the dopaminergic terminals were selectively destroyed by 6-hydroxydopamine. Calibration of the basal oxidation current revealed that the extracellular dopamine concentration was 26 nM. Brief and moderate electrical stimulation of the nigrostriatal pathway at the level of the medial forebrain bundle induced a large increase in the dopamine current. The observed elevation in the dopamine signal lasted as long as the stimulation. It varied with the frequency (0-25 Hz) of the pulses in an exponential manner. Stimulation pulses distributed in a bursted pattern were twice as potent as an equivalent number of pulses regularly spaced. High frequency stimulations (50 Hz) were also investigated in anaesthetized rats (without pargyline) with untreated carbon fiber electrodes; they induced a very large increase in the dopamine extracellular concentration (up to 8-15 microM). Interruption of the dopaminergic impulse flow either by an electrolytic lesion or by a low dose of apomorphine (0.05 mg/kg) caused an immediate decrease of the dopamine current. The time courses and amplitudes (-70%) of these effects were identical. Subsequent injection of haloperidol (0.5 mg/kg) reversed the apomorphine effect up to +360% of the control basal value. Administration of dopaminergic antagonists such as haloperidol (0.05 and 0.5 mg/kg) or metoclopramide (2 mg/kg) significantly increased the dopamine current up to 317, 340 and 215% of the respective control values. Nomifensine (4 mg/kg) produced a big increase (+417%) of the extracellular dopamine levels. The effect of electrical stimulation of the dopaminergic pathway was potentiated by drugs such as amphetamine (2 mg/kg), nomifensine (4 mg/kg) or haloperidol (0.05 and 0.5 mg/kg) but was not altered by apomorphine (0.05 mg/kg). The study by in vivo voltammetry of the variations in the striatal extracellular dopamine concentrations shows that the release of dopamine is under the influence of both the frequency of impulse flow and of dopaminergic striatal autoreceptors.