Central effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in mice.

The central effects of endothelin-1 (ET-1, 0.5, 1, 2.5 and 10 pmol/mouse) and endothelin-3 (ET-3, 2.5, 5, 10, 20 and 25 pmol/mouse) have been studied after intracerebroventricular (i.c.v.) administration in mice. The following methods were used: behavioral observations, rotarod, spontaneous and amphetamine-stimulated motor activity, and hexobarbital-induced narcosis. ET-1 and ET-3 evoked a dose-dependent behavioral syndrome with a short excitatory period in the higher doses lasting for 5-10 min, followed by a prolonged depressive phase (about 90 min). ET-1 and ET-3 produced central depressive effects demonstrated by depressive behavior signs, decrease of the spontaneous and amphetamine-stimulated motor activity, and prolongation of the hexobarbital-induced narcosis.