CHARACTERIZATION OF METHYLPHENIDATE AND NOMIFENSINE INDUCED DOPAMINE RELEASE IN RAT STRIATUM USING INVIVO BRAIN MICRODIALYSIS

The in vivo effects of methylphenidate (50 mg/kg) and nomifensine (20 mg/kg) on dopamine release and metabolism in the rat striatum were studied using brain microdialysis. Dialysate catecholamine content was measured by high pressure liquid chromatography with electrochemical detection. Both compounds increased the dialysate content of dopamine (430% and 320% of basal efflux, respectively). Release was inhibited by reducing extracellular calcium levels and by infusion of tetrodotoxin (2-mu-M) via the dialysis probe (calcium free - 39 +/- 18% of control, methylphenidate; 40 +/- 17% of control, nomifensine; tetrodotoxin -35 +/- 19% of control, methylphenidate; 40 +/- 14% of control, nomifensine) and also by prior depletion of dopamine storage pools using reserpine (5 mg/kg) (15 +/- 12% of control, methylphenidate; 19 +/- 9% of control, nomifensine). Dialysate levels of dihydroxyphenylacetic acid were not altered by either drug whereas homovanillic acid levels increased. These data suggest that both drugs increase dialysate dopamine content by facilitating Ca2+-dependent vesicular release most probably by inhibition of dopamine reuptake.