POSSIBLE INVOLVEMENT OF THE ACTIVATION OF VOLTAGE-SENSITIVE CALCIUM CHANNELS IN THE AMELIORATING EFFECTS OF NEFIRACETAM ON SCOPOLAMINE-INDUCED IMPAIRMENT OF PERFORMANCE IN A PASSIVE-AVOIDANCE TASK

We investigated the effects of various types of calcium channel antago nists on the amelioration by nefiracetam [N-(2,6-dimethylphenyl)-2-(2- oxo-1-pyrrolidinyl) acetamide, DM-9384] of scopolamine-induced impairm ent of performance in a passive avoidance task in mice. The reversal o f the scopolamine-induced impairment of performance by nefiracetam sho wed a bell-shaped plot. Both i.p. and i.c.v. injection of L-type calci um channel antagonists such as nifedipine and flunarizine attenuated t he ameliorating effects of nefiracetam, although diltiazem had no effe ct. Neomycin, an N-type calcium channel antagonist, also attenuated th ese effects of nefiracetam in a dose-dependent manner. Further, LaCl3 but not NiCl2 showed inhibitory effects on the amelioration by nefirac etam. These results suggest that the activation of high-voltage-activa ted, :but not low-voltage-activated, calcium channels is involved in t he ameliorating effects of nefiracetam on scopolamine-induced impairme nt of performance in a passive avoidance task.