Objective: To evaluate the effect of low dose naloxone on remote seizure susceptibility after repeated febrile seizures(FS) in developing age.
Methods: Warm water induced rat FS model was developed in this study. Forty-nine SD rats were randomly divided into two groups: normal control group(n=10) and hyperthermic seizure group (n=39). The latter was further divided into FS control group (n=13) and naloxone-treated group (n=26). The dose of naloxone was different in the two naloxone-treated groups (13/each group). One group dose was 1 mg/kg, and the other 2 mg/kg. Each rat of hyperthermic seizure groups was induced to have 7 febrile seizures at the interval of 1 day. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of other groups were injected with 0.9% sodium chloride. After the seventh stimulation, all rats were left un-stimulated for 2 months, then re-stimulated. Re-stimulated seizure incidence rate, seizure duration and seizure grade in different groups were observed and compared with each other. Hippocampal mossy fiber sprouting was detected by Timm stain.
Results: In naloxone-treated group, the rats' seizure duration and seizure grade [(5.66+/-2.78) min, (2.97+/-1.18)] significantly decreased (t=5.035, P<0.01; t=3.343, P<0.01) compared with those in FS control group [(21.18+/-4.06) min, (4.54+/-0.78)], although no significant gap was observed on seizure incidence rate(57.7%,84.6% respectively) and seizure latency between them. In non-treated group, in which two rats developed status epilepsy, the incident rate of the fifth grade seizure was 69.3%, much higher than 19.3% of naloxone treated group. Timm-stain pattern showed that the straining in the IML (inner molecular layer) of treated group rats was much lighter than that of non-treated group [(2.33+/-1.03), (0.92+/-0.79), P<0.01].
Conclusion: Low dose naloxone used on naive rat with repeated febrile seizures can efficiently decrease the seizure susceptibility in the mature period and lighten the neural damage by twice-hit seizure in the mature period as well.