CONTINUOUS IN-VIVO MONITORING OF EVOKED DOPAMINE RELEASE IN THE RAT NUCLEUS-ACCUMBENS BY AMPEROMETRY

The release of dopamine in the nucleus accumbens of anaesthetized rats was evoked either by electrical stimulation of the mesolimbic dopaminergic pathway or by local ejection of N-methyl-D-aspartate in the ventral tegmental area. Untreated carbon-fibre electrodes implanted in the nucleus accumbens were held at +400 mV versus a reference electrode, and the oxidation current was continuously monitored. Despite a poor selectivity to dopamine versus other oxidizable compounds such as ascorbic acid, the evoked responses were solely due to dopamine overflow in the extracellular fluid since they were closely correlated with the stimulations and exhibited all the expected characteristics related to a dopamine release. First, these effects were closely consistent with the anatomy of the mesolimbic dopaminergic system. Second, the responses to electrical stimulations were abolished by a tetrodotoxin ejection in the vicinity of the carbon-fibre electrode and they were strongly, but reversibly, diminished (60% decrease) when cadmium was substituted for calcium in an artificial cerebrospinal fluid ejected dose to the electrode. Third, their maximal amplitudes were enhanced by amphetamine, pargyline, nomifensine and haloperidol. Fourth, inhibition of dopamine reuptake by nomifensine induced a five-fold decrease in the rate of decline of the evoked oxidation current. Fifth, contribution of noradrenaline and serotonin to the observed effects seems unlikely since specific reuptake blockers (desipramine and sertraline, respectively) did not alter them. Dopaminergic neurons discharge either in a single spike mode with a mean firing rate below 5 Hz or in a bursting pattern (intraburst frequency: 10 to 20 Hz). We show here that after a single pulse stimulation dopamine is released and eliminated within 200 ms and that the maximal dopamine overflow evoked by a train of six pulses at 20 Hz was five-times higher than that evoked by a single pulse. These observations are in line with the importance of the bursting pattern in the efficiency of dopaminergic transmission.