Like
dexamphetamine, SKF38393 induces an increase in striatal
dopamine efflux which is insensitive for
tetrodotoxin, Ca(2+) independent and prevented by a
dopamine transporter inhibitor. The dexamphetamine-induced striatal
dopamine efflux originates from both the reserpine-sensitive vesicular
dopamine pool and the alpha-methyl-para-tyrosine-sensitive
cytosolic dopamine pool. Given the similarities between
dexamphetamine and SKF38393, we hypothesized that both types of pool also contribute to the striatally applied SKF38393-induced
dopamine efflux. Using in vivo
microdialysis technique, we analysed the contribution of these pools to the SKF38393-induced striatal
dopamine efflux in freely moving rats. The increase of
dopamine efflux induced by 1.5mug SKF38393 was largely prevented by either
reserpine (5mg/kg i.p., given 24h earlier) or alpha-methyl-para-tyrosine (250mg/kg i.p., given 2h earlier), showing that both the vesicular
dopamine pool and the
cytosolic dopamine pool contribute to the SKF38393-induced increase in striatal
dopamine efflux. The sum of the amounts of
dopamine that was sensitive to either
reserpine or alpha-methyl-para-tyrosine, was greater than 100%, namely 137.6% of the basal
dopamine level and 143.9% of the SKF38393-induced
dopamine level, suggesting that striatally applied SKF38393 promotes the redistribution of
dopamine from vesicles to the
cytosol, and vice versa. The finding that the combined treatment of
reserpine and alpha-methyl-para-tyrosine only inhibited the SKF38393-induced striatal
dopamine efflux till 86.0% of the control, is ascribed to the notion that SKF38393 can also inhibit the
re-uptake of
dopamine. The latter conclusion has far-reaching consequences for studies in which the effects of SKF38393 are simply ascribed to its
dopamine D(1) receptor stimulation capacity.
