Mechanisms underlying domoic acid-induced dopamine release from striatum: an in vivo microdialysis study

Abstract

The brain microdialysis technique has been used to examine the in vivo effects of the neurotoxin domoic acid (an ionotropic glutamate receptor agonist) on dopamine (DA) release in the striatum of conscious and freely moving rats. Local application of domoic acid (500 microM) through the microdialysis probe produced an increase in striatal DA content (597 +/- 96% with respect to basal levels). The release of DA induced by domoic acid was not attenuated in a Ca(+2)-free medium (469 +/- 59%) or after pretreatment with 10 mg/kg reserpine (533 +/- 79%). Intrastriatal infusion of 1 microM tetrodotoxin (TTX) partially reduced the domoic acid-evoked DA release (278 +/- 34%). Moreover, domoic acid perfusion had no effect on K+-evoked DA release. The results suggest that domoic acid increases the striatal DA release according to a reserpine-independent, calcium-independent and partially TTX-insensitive mechanism, suggesting that these effects probably involve a nonexocytotic process. On the other hand, the inhibitor of DA uptake nomifensine (10 microM) reduced the domoic acid-evoked DA release (356 +/- 59%), suggesting that a carrier-dependent mechanism could be involved in the effect of domoic acid on the striatal DA levels.