Presynaptic autoinhibition of the electrically evoked dopamine release studied in the rat olfactory tubercle by in vivo electrochemistry

Abstract

Evoked dopamine release was monitored in vivo from the olfactory tubercle of anaesthetized rats by differential pulse amperometry combined with carbon fibre electrodes which, in most cases, were electrochemically treated. Dopamine release was evoked by electrical stimulation of the ascending dopaminergic pathway. The dopamine release evoked by burst stimulation (20 s with a mean frequency of 6 Hz) was dose-dependently decreased by D,L-apomorphine (25-800 micrograms/kg, s.c.) or by quinpirole (50 micrograms/kg, s.c.) while the opposite effect was observed with haloperidol (12.5 micrograms/kg-0.5 mg/kg, s.c.) or with D,L-sulpiride (2-200 mg/kg, s.c.). Neither the D1 agonist SKF 38393 (10 mg/kg, s.c.) nor the D1 antagonist SCH 23390 (0.5 mg/kg, s.c.) affected the evoked dopamine release. Moreover, sulpiride competitively antagonized the effects of apomorphine. The relative amplitude of the apomorphine inhibition was inversely correlated with the stimulation frequency (6 or 9 Hz). The increase induced either by haloperidol or by sulpiride was positively related to the stimulation frequency (from 3 to 9 Hz) and reached a stable value (+700% of the pre-drug-evoked dopamine release) with higher frequencies (from 9 to 20 Hz). This increase also depended on the duration of the stimulation: both single-train (10 pulses) or burst stimulations for 20 s, whose frequency inside the trains was in both cases 14 Hz, evoked a dopamine release which was minimally affected by sulpiride or haloperidol. In conclusion, in physiological conditions the amplitude of the impulse flow-dependent dopamine release is regulated by the extrasynaptic extracellular dopamine concentration which varies from 10 to 100 nM. This presynaptic autoinhibition is mediated by autoreceptors of the D2 type and is involved in the nonlinear relationship between impulse flow and dopamine release.