Differences in evoked dopamine efflux in rat caudate putamen, nucleus accumbens and tuberculum olfactorium in the absence of uptake inhibition: influence of autoreceptors.

1. Dopamine efflux following single pulse or train of pulse stimulations was measured in slices of rat caudate putamen, nucleus accumbens and tuberculum olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1, 5, 10, 20 or 50 pulses were applied at each location at frequencies varying from 10 Hz to 500 Hz. 2. There are significant differences in the ability of the different regions to increase dopamine efflux following single or repeated electrical stimulation. 3. Highest release in response to a single pulse is observed in the caudate putamen (approximately 250 nM dopamine), but the ratio of the peak dopamine overflow following a train of 20 pulses (50 Hz) when compared to a single pulse is rarely greater than three. 4. Release following single pulse stimulation in the nucleus accumbens (approximately 185 nM dopamine) is often slightly less than in the caudate putamen, but the ratio of peak release when trains of 20 pulses (50 Hz) are compared to single pulse stimulation has been as great as seven fold. 5. The tuberculum olfactorium releases the least dopamine of the three regions following a single pulse stimulation (approximately 40 nM dopamine), but the ratio of peak dopamine release following trains of 20 pulses (50 Hz) when compared to single pulse can result in a value approaching 20. 6. When 20 pulses are applied to the caudate putamen at frequencies ranging from 10 to 500 Hz, the peak efflux is essentially the same (frequency/release profile is flat), with the maximum increase only 140% that of a single pulse.7. By contrast, in the nucleus accumbens and the tuberculum olfactorium, well defined frequencyrelease relationships are seen following 20 pulses applied at 10, 20 and 50 Hz; at higher frequencies the dopamine release decreases as frequency is increased.8. Experiments with sulpiride or metoclopramide (dopamine D2 receptor antagonists) indicate that dopamine release in the caudate putamen is not regulated by dopamine autoreceptor activation by endogenous dopamine under our experimental conditions (in the absence of reuptake inhibtion). By contrast, in the nucleus accumbens and in the tuberculum olfactorium, we present evidence to show that at frequencies of stimulation up to 20 Hz, endogenous dopamine acts at dopamine autoreceptors to inhibit further release of dopamine but a minimum exposure time of between 500 and 1000 ms is needed for the response to D2 autoreceptor activation by endogenously released dopamine to be seen.