Effects of the neoclerodane Hardwickiic acid on the presynaptic opioid receptors which modulate noradrenaline and dopamine release in mouse central nervous system

Abstract

We have comparatively investigated the effects of Hardwickiic acid and Salvinorin A on the K+-evoked overflow of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from mouse hippocampal and striatal nerve terminals, respectively. The K+-evoked overflow of [3H]DA was inhibited in presence of Salvinorin A (100nM) but not in presence of Hardwickiic acid (100nM). Hardwickiic acid (100nM) mimicked Salvinorin A (100nM) in facilitating K+-evoked hippocampal [3H]NA overflow and the two compounds were almost equipotent. Facilitation of [3H]NA overflow caused by 100nM Hardwickiic acid was prevented by the κ-opioid receptor (KOR) antagonist norbinaltorphimine (norBNI, 100nM) and by the selective δ-opioid receptor (DOR) antagonist naltrindole (100nM), but was not altered by 100nM D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), a selective μ-opioid receptor (MOR) antagonist. We conclude that Hardwickiic acid modulates hippocampal [3H]NA overflow evoked by a mild depolarizing stimulus by acting at presynaptic opioid receptor subtypes.