CENTRAL EFFECT 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/mou se) and endothelin-3 (ET-3, 2.5, 5, 10, 20 and 25 pmol/mouse) have bee n studied after intracerebroventricular (i.c.v.) administration in mic e. The following methods were used: behavioral observations, rotarod s pontaneous and amphetamine-stimulated motor activity and hexobarbital- induced narcosis. ET-1 and ET-3 evoked a dose-dependent behavioral syn drome 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 depressi ve behavior signs, decrease of the spontaneous and amphetamine-stimula ted motor activity, and prolongation of the hexobarbital-induced narco sis.