[Flunarizine and sabeluzole improves behavior disorders caused by cold-induced cortical lesions in mice]

The present paper reports two experiments is which an effect of sabeluzole and flunarizine upon behavioural consequences reflecting ischemic damage following cortical freezing lesions was evaluated in NMRI female mice. The parietal lesion was performed by applying a flat (2 mm in diameter) of a metal probe cooled to -75 degrees C on the exposed skull for 5 s. Flunarizine (15 mg/kg) was administered sc 1 hr before and 4 hr after performing the lesion and then, 1 mg/kg p.o. once daily for 14 days. Sabeluzole (5 mg/kg) was administered p.o. 1 hr before and 5 hr after performing the lesion and then, 5 mg/kg p.o. once daily for 14 days. Hole--board method was used to evaluate the exploratory head-dips activity of an animal in 5 sessions separated by 24 hr intervals during the postlesion testing from the 20th to the 24th day, i.e. from day 6 to 10 after finishing the treatment. The session lasted 5 min. In both experiments, the mean number of exploratory hole visits in lesioned female mice was significantly increased. Both flunarizine and sabeluzole reduced high hole exploration of lesioned mice to levels corresponding to those of the controls. Neither flunarizine nor sabeluzole affected significantly exploratory hole visit of control animals. Results showed that flunarizine as well as sabeluzole ameliorated behavioural disturbances reflecting the brain impairment induced through cortical freezing lesion. This effect is most probably related to the protective effect of both drugs against hypoxia induced in laboratory animals by several experimental procedures. The hole--board method seems to be suitable for the screening of compounds considered as cerebroprotective drugs.