Stimulation of postsynaptic D2− dopamine receptors by B-HT 958 is revealed by co-treatment with the D1− receptor agonist SKF 38393

Abstract

The motor activity of reserpine-treated mice was used to study effects of B-HT 958 (2-amino-6-(p-chlorobenzyl)-4H-5,6,7,8-tetrahydrothiazolo-[5,4-d]- azepine) on postsynaptic dopamine and noradrenaline receptors. The motor activity was only slightly stimulated by B-HT 958 or by the D1- receptor agonist SKF 38393 but it was markedly increased by the two drugs given in combination. The effect of B-HT 958 peaked earlier following low rather than high doses. The enhanced motor activity was inhibited by the D2- receptor antagonist sulpiride or the D1- receptor antagonist SCH 23390, indicating that it was caused by stimulation of both receptor types. The results suggest that B-HT 958 stimulates postsynaptic D2- receptors in addition to D2- autoreceptors and that its blockade of postsynaptic alpha 2-adrenoceptors is of no importance for the motor activity.