EFFECTS OF RILUZOLE ON RAT CORTICAL-NEURONS - AN IN-VITRO ELECTROPHYSIOLOGICAL STUDY

1 The electrophysiological effects of riluzole on rat prefrontal and f rontal cortical neurones were investigated by using both extracellular (field) and intracellular recording techniques in brain slices. 2 Bat h applied riluzole (3-200 mu M) depressed the cortico-cortical stimulu s-evoked field potential in a concentration-related manner (EC(50) = 2 9.5 mu M). 3 Riluzole (3-100 mu M) reduced the tonic firing of the neo cortical neurones which was caused by intracellular current injection, while it did not have any effect on the resting membrane potential an d apparent input resistance of these cells. 4 In the presence of tetro dotoxin (1 mu M) and tetraethylammonium (30 mM), the injection of a de polarizing current step generated a calcium spike in the neocortical n eurones. Riluzole (30 mu M) abolished this calcium-dependent action po tential. However, when the amount of the depolarizing current was incr eased the calcium-dependent regenerative potential was evoked again. 5 The depolarization of the membrane (10-20 mV) caused by brief (8-15 s ) bath applications of glutamate (300 mu M-1 mM) were not changed in t he presence of riluzole (30 mu M). 6 It is concluded that riluzole has direct actions on rat neocortical neurones: (a) it blocks the repetit ive discharge of sodium action potentials and (b) it increases the thr eshold for the generation of the calcium spike. These two cellular mec hanisms might at least in part account for the depression of the corti cocortical field potential caused by this drug.