Ethanol-induced, nonexocytotic [ 3H]dopamine release from rat nucleus accumbens slices

Abstract

This study was designed to investigate whether a carrier-dependent mechanism is involved in ethanol-induced dopamine release in vitro. Rat nucleus accumbens slices were incubated with [ 3H]dopamine in the presence of pargyline and then superfused. Spontaneous [ 3H]dopamine release was unaffected by addition of tetrodotoxin or withdrawal of calcium, but was increased significantly with treatment with nomifensine, a dopamine transporter blocker. Exposure of the slices to electrical field stimulation (bipolar pulse, 2-ms long, 20 mA, 0.5 Hz for 4 min), high potassium concentration (30 mM, 2 min), or ethanol (25–100 mM, 2 min) was associated with increased [ 3H]dopamine release. With addition of tetrodotoxin or withdrawal of calcium from the perfusion medium, a 75% or greater inhibition of electrically or high potassium concentration–evoked [ 3H]dopamine release was observed, but ethanol-induced [ 3H]dopamine release was not altered. Treatment with nomifensine potentiated electrically or high potassium concentration–evoked [ 3H]dopamine release, but inhibited the effects of ethanol on [ 3H]dopamine release from the nucleus accumbens slices. The results indicate that the mechanism underlying the effects of ethanol is different from that underlying the effects of depolarization with electrical stimulation or high potassium concentration and support the suggestion that a nonexocytotic, carrier-mediated mechanism may be involved in ethanol-evoked dopamine release in vitro.