Functional cooperation between neurosteroids and D2 dopamine antagonists on KCl-evoked [3H]noradrenaline release: modulation by calcium channel blockers.

It has recently been proposed that neurosteroids, such as dehydroepiandrosterone sulphate and pregnenolone sulphate, interfere with the dopamine system in the central nervous system. According to our previous report showing that the butyrophenone, spiperone, slightly enhances the evoked release of [3H]-noradrenaline ([3H]NA) in the presence of these sulphated steroids, the present study was carried out to document the putative interplay between steroids and spiperone, which is known to be a prototypic D2 dopamine antagonist and also a 5-HT2 serotonin antagonist. For this purpose, the paradigm of KCl-evoked [3H]NA release from preloaded rat hippocampal slices was used to investigate the interactions between neurosteroids, spiperone and the voltage-sensitive calcium channels (VSCCs). The selective 5-HT2 serotonin antagonist ritanserine was ineffective, whereas sulpiride, a selective D2 dopamine antagonist mimicked the action of spiperone, thus suggesting that the blockade of D2 dopamine receptors accounted for the modulatory effect of spiperone on neurosteroid-induced modulation of evoked [3H]NA release. In addition, this facilitation of KCl-evoked [3H]NA release by the combination of a steroid and a D2 dopamine antagonist was partially inhibited by the L- and N-type VSCC blockers nifedipine and omega-conotoxin GVIA, respectively. The present results provide in-vitro functional evidence for the putative role of VSCCs in the interplay between steroids and D2 dopamine receptors.