BEHAVIOR OF MESOCORTICAL DOPAMINE TERMINALS DURING SINGLE AND REPETITIVE STIMULATION - COMPARISON WITH NIGROSTRIATAL NEURONS

The present study reinvestigates the role of autoinhibition in dopamin e (DA) release from mesoprefrontal and nigrostriatal DA neurons using improved methodology. Slices of rabbit prefrontal cortex (PFC) and str iatum (STR) were labeled with [H-3]DA and superfused in the presence o f nomifensine (3 mu M). Overflow was elicited by field stimulation wit h 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 overflow 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 a t 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 conside rably smaller, and the per-pulse release at higher frequencies was muc h larger than in the STR. The DA D-2-receptor antagonist sulpiride (3 mu M) enhanced pulse-train-evoked overflow from the STR at all frequen cies between 0.3 and 10 Hz, whereas facilitation in the PFC was achiev ed at 10 Hz only. One-pulse-evoked overflow was not facilitated by sul piride in either region. In conclusion, DA overflow from PFC terminals is not generally higher than overflow from STR terminals, as suggeste d in earlier studies. Larger per-pulse overflow from mesoprefrontal DA neurons occurs only under intense stimulation and is only in part a c onsequence of weak autoinhibition in this region.