Global cerebral ischemia leads to selective neuronal damage in the CA1
sector of the hippocampus and in the dorsolateral striatum. In additi
on, it results in deficits in spatial learning and memory as shown by
an increase in escape latency and swim distance during the escape tria
ls and a reduction of time spent in the quadrant of the former platfor
m position during the probe trial of the water maze. Flupirtine is a n
on-opioid, centrally acting analgesic which has been shown to be neuro
protective against N-methyl-D-aspartate (NMDA)-mediated toxicity in vi
tro. The purpose of the present study was to investigate the potential
protective effect of flupirtine in vivo with both behavioural and his
tological measures of global cerebral ischemia. Global ischemia was in
duced by four-vessel-occlusion (4VO) for 20 min in rats. Flupirtine wa
s administered at a dose of 5 mg/kg i.p. either 20 min before and 50 m
in after occlusion (pre-treatment) or directly and 70 min after occlus
ion (post-treatment). 1 week after surgery, spatial learning and memor
y was tested in the Morris water maze. Pre-treatment with flupirtine r
educed the increase in escape latency and in swim distance induced by
4VO. It also diminished the deficit in spatial memory as revealed by a
n increase in time spent in the quadrant of the former platform positi
on during the probe trial which was reduced by 4VO. Post-treatment wit
h flupirtine had no effect on the deficits in spatial learning and mem
ory induced by 4VO. Neuronal damage in the CA1 sector of the hippocamp
us and in the striatum produced by 4VO was significantly attenuated wi
th pre-treatment of flupirtine whereas post-treatment did not affect t
his neuronal damage. The present data demonstrate that pre-treatment w
ith flupirtine exerts a protective effect on hippocampal and striatal
neuronal damage and on deficits in spatial learning induced by 4VO. (C
) 1997 Elsevier Science B.V.