ABSTRACT
The mechanism involved in the regulation of dopamine (DA) rease from mesocortical dopaminergic neurons were studied. Prefrontal cortical slices (PFC) were incubated with 3H-Da in the presence of 0.3 uM desipramine. Under these conditions,6 to 10% of 3H-norepinephrine was formed. After incubation, the slices were superfused (2 slices/chamber). At 45 minutes of washout, a constant rate of efflux of 3H- norepinephrine was obtained; 1.46+/- 0.1 % of the 3H present in the slices was released every 5 minutes. Electrical stimulation (1Hz, 120 pulses) produced a calcium dependent increase in the outflow of 3H- products above prestimulation levels (3.4+/_ 0.1%) Since the release of a neurotransmitter may be modulated by presynaptic receptors others than autoreceptors, we investigated the pharmacology of presynaptic receptors monitoring the effects of DA, norepinephrine, serotonine, acetylcholine, Gaba and CCK agonists and antagonists on the electrically evoked relase of DA. Apomorphine, LY171555 and bromocriptine inhibited Da realese. Maximun inhibition of release values for these drugs were 66 and 59% (EMAX) and those for EC50 were 25, 29 and 20 nM, respectively. Haloperidol antagonized the inhibitory effect of DA agonist whereas phentolamine hsd no effect. Haloperidol produced singnificant increase in the stimulation- evoked release of 3H (76%). The other agents did not modify DA release from PFC slices. These results suggest that DA release is modulated by auyoreceptors whereas the presynaptic noradrenergic, cholinergic serotoninergic, Gabaergic and CCK receptors do not appear to play a significant role in the regulation of DA