Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry.

Mesolimbic dopaminergic neurons discharge either in a single spike mode or in a bursting pattern. In order to investigate the influence of these patterns on dopamine release, extracellular dopamine was electrochemically monitored in vivo in the olfactory tuberculum of anaesthetized rats by means of two approaches. In the first, a pure signal, unequivocally corresponding to extracellular dopamine, was recorded every minute from pargyline treated rats by differential normal pulse voltammetry combined with electrochemically treated carbon fibre electrodes. In the second, the differential current solely due to oxidation of all the catechols was monitored every 1 s in drug-free rats by differential pulse amperometry. In basal conditions this current was mainly due to extracellular DOPAC. However, electrical stimulation of the dopaminergic pathway for 20 s elicited an immediate increase in this signal. This effect was due to evoked dopamine release since it was strongly enhanced by amphetamine (2 mg/kg) or pargyline (75 mg/kg) injections. As studied with both approaches, the evoked increase in extracellular dopamine concentration was immediate and lasted as long as the stimulation. The amplitude of the effect depended on the frequency of the stimulation (from 3 to 14 Hz) in an exponential manner but never exceeded 1 microM dopamine. Bursting stimulations (frequency within the trains: 14 Hz) were twice as potent as regularly spaced ones, having the same average frequency (5 Hz). In conditions which mimicked the spontaneous activity of dopaminergic neurons when they switch from one pattern to the other (4 Hz regularly spaced stimulation versus trains at a mean frequency of 6 Hz), the bursting stimulations were found to be up to 6 times more potent. Therefore, as regards the functional efficacy of DA neurons, bursting might be much more important than mean firing frequency.