Effect of potassium channel modulators in mouse forced swimming test

1 The effect of intracerebroventricular (i.c.v.) administration of differen t potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gl iquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimmi ng test, an animal model of depression. 2 Tetraethylammonium (TEA; 5 mu g per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 mu g per mouse i.c.v.) and gliquidone (6 mu g pe r mouse i.c.v.) administered 20 min before the test produced anti-immobilit y comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg(-1) s.c.) and imipramine (30 mg kg(-1) s.c.). 3 By contrast pinacidil (10-20 mu g per mouse i.c.v.), minoxidil (10-20 mu g per mouse i.c.v.) and cromakalim (20-30 mu g per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. 4 Repeated administration of an antisense oligonucleotide (aODN) to the mKv 1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-depende nt increase in immobility time of mice 72 h after the last injection. At da y 7, the increasing effect produced by aODN disappeared. A degenerate mKv1. 1 oligonucleotide (dODN), used as control, did not produce any effect in co mparison with saline- and vector-treated mice. 5 At the highest effective dose, potassium channels modulators and the mKv1 .1 aODN did not impair motor coordination, as revealed by the rota rod test , nor did they modify spontaneous motility as revealed by the Animex appara tus. 6 These results suggest that modulation of potassium channels plays an impo rtant role in the regulation of immobility time in the mouse forced swimmin g test.