Effects of combined nimodipine and metrifonate on rat cognition and cortical EEG.
The present study investigated if short-term treatment with an L-type Ca2+-channel inhibitor, nimodipine, can stimulate cognitive functioning and cortical electroencephalograph (EEG) arousal, and potentiate the effect of a cholinesterase inhibitor, metrifonate. Pretraining administration of nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on water maze and passive avoidance behavior of young neurologically intact controls, or water maze and passive avoidance performance failure induced by scopolamine pretreatment (i.p.; 0.4 mg/kg during the water maze and 2.0 mg/kg during the passive avoidance study), medial septal lesioning, or aging. Furthermore, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on the improvement by metrifonate (10 mg/kg, p.o.) of the water maze and passive avoidance failure induced by scopolamine pretreatment or medial septal lesioning, nor did it affect the potential of metrifonate (30 mg/kg. p.o.) to improve the water maze or passive avoidance behavior of aged rats. Finally, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on spontaneously occurring thalamically generated neocortical high-voltage spindles or spectral EEG activity of young controls, nor did it alleviate the spectral EEG abnormality induced by scopolamine (0.2 mg/kg, i.p.) administration. Also, the combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10 mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced spectral EEG activity abnormalities. According to the present results, short-term treatment with nimodipine does not stimulate cognitive functions or increase cortical EEG arousal, and does not block or potentiate the propensity of metrifonate to improve cognitive performance of rats.
Jäkälä
P
P
Department of Neuroscience and Neurology, University of Kuopio, Finland. pekka.jakala@uku.fi
Riekkinen
M
M
Björklund
M
M
Koivisto
E
E
Schmidt
B
B
Riekkinen
P
P
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology; D014236:Trichlorfon / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D009553:Nimodipine; D014236:Trichlorfon; D012601:Scopolamine