Effects of non-NMDA receptor modulators on [3H] dopamine release from rat mesencephalic cells in primary culture

The effects of AMPA and kainate on [3H]dopamine release from fetal (embryonic day 15) rat mesencephalic neurons in primary culture were enhanced markedly in a dose-dependent fashion by cyclothiazide, a recently described inhibitor of AMPA receptor desensitization. The EC50 value for cyclothiazide was 2.2 +/- 0.8 microM. The release of [3H]dopamine induced by both AMPA (or kainic acid) and the combination of AMPA (or kainic acid) with cyclothiazide was antagonized by specific antagonists like 6-cyano-7-nitroquinoxaline-2,3-dione or the noncompetitive benzodiazepine GYKI 52466. Unlike cyclothiazide, the lectin concanavalin A did not stimulate [3H]dopamine release. These results established the involvement of AMPA-preferring receptors on [3H]dopamine release from rat mesencephalic neurons in primary culture and provided further evidence for the existence of regulatory allosteric sites on AMPA receptor subunits.