Ameliorative effects of tamolarizine on place learning impairment induced by transient forebrain ischemia in rats.
In the present study we investigated the effect of (+/-)-1-(3, 4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride (tamolarizine), a calcium entry blocker, on place learning impairment in rats with damage selective to the hippocampal CA1 subfield induced by transient forebrain ischemia. Tamolarizine was administered (40 mg/kg) immediately after 15-min brain ischemia. Place learning was tested in a task in which the rat was required to alternatively visit two places located diametrically opposite each other in an open field. The ischemia+saline group showed severe learning impairment in this task; their performance level was significantly inferior to that of the sham-operated group through the test period (30 days). Although the ischemia+tamolarizine group showed slight impairment of place learning during the course of this test, they later reached almost the same performance level as the sham-operated group. Selective neuronal loss in the CA1 subfield was much less in the ischemia+tamolarizine group than in the ischemia+saline group. These results indicate that tamolarizine treatment protects the hippocampus from ischemic brain damage and ameliorates place learning impairment.
Tamura
R
R
Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Japan.
Nakada
Y
Y
Nishijo
H
H
Miyake
N
N
Ono
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012653:Self Stimulation; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D010879:Piperazines; C050134:tamolarizine