Behavior of mesocortical dopamine terminals during single and repetitive stimulation: comparison with nigrostriatal...

The present study reinvestigates the role of autoinhibition in dopamine (DA) release from mesoprefrontal and nigrostriatal DA neurons using improved methodology. Slices of rabbit prefrontal cortex (PFC) and striatum (STR) were labeled with [3H]DA and superfused in the presence of nomifensine (3 microM). Overflow was elicited by field stimulation with a single pulse (autoinhibition-free condition) or trains of pulses (4, 16 and 64) delivered at 0.05 to 30 Hz. One-pulse stimulation caused a measurable overflow of tritium in the PFC and STR (0.12% vs. 0.21% of tissue tritium, respectively). At increasing numbers of pulses, per-pulse over-flow decreased at all frequencies, but it was consistently more pronounced in the STR than in the PFC (e.g., 64 pulses/3 Hz: -30% PFC, -70% STR). The frequency dependence of DA release was biphasic at all numbers of pulses with overflow largest at 0.05 Hz and smallest at 3 Hz. In the PFC, however, the magnitude of the changes was considerably smaller, and the per-pulse release at higher frequencies was much larger than in the STR. The DA D2-receptor antagonist sulpiride (3 microM) enhanced pulse-train-evoked overflow from the STR at all frequencies between 0.3 and 10 Hz, whereas facilitation in the PFC was achieved at 10 Hz only. One-pulse-evoked overflow was not facilitated by sulpiride in either region. In conclusion, DA overflow from PFC terminals is not generally higher than overflow from STR terminals, as suggested in earlier studies. Larger per-pulse overflow from mesoprefrontal DA neurons occurs only under intense stimulation and is only in part a consequence of weak autoinhibition in this region.