PHARMACOLOGICAL MODULATION OF ENDOGENOUS DOPAMINE AND DOPAC OUTFLOW FROM NUCLEUS-ACCUMBENS

The release of endogenous DA and DOPAC from nucleus accumbens slices w ere studied measuring net outflow of DA and DOPAC in the superfusate o f static chambers, to analyze the correlation between DA and DOPAC out flows and identify which DA stores may serve as possible sources for D OPAC formation. Under resting conditions, or following stimulation wit h low (<15 mM) KCI concentration, DOPAC outflow was greater than DA. W hen DA release was stimulated by higher (>25 mM) KCI concentrations, D A outflow increased, proportionally more than DOPAC. In the virtual ab sence of Ca2+ in the Krebs solution DA outflow, induced by 25 mM KCl, was reduced to about 10%, while DOPAC outflow was only reduced to 45%. When the synthesis of DA was inhibited with alpha-MPT, DA and DOPAC o utflow were unchanged during the first stimulation period. During a se cond stimulation period, however, their outflow were significantly red uced. Nomifensine, a DA uptake inhibitor, increased the basal DA outfl ow by about 100%, but only blocked DOPAC basal outflow by about 25%. T he 25 mM KCI stimulated DA outflow was not affected by Nomifensine, wh ile the stimulated DOPAC outflow was reduced by about 50%. These resul ts demonstrate that there is a weak correlation between the outflows o f DA and DOPAC, suggesting a complex relationship between the mobiliza tion of the different DA pools and DOPAC outflow. The formation of DOP AC from some of these pools, appear to be dependent on the stimulation levels and on the pharmacological manipulation of the tissue.