Objective To explore the effects and possible neural mechanisms of naloxone on learning and memory ability in rats with repeated febrile seizures (FS). Methods The warm water was adopted to induce rats FS model and to induce 21-days-old SD rats seizure one time every day, continuous up to 10 times.The rats were injected intraperitoneally with naloxone (1 mg/kg)immediately after FS occurred in naloxone-treated group(NT group, n=14), while the rats of FS-control group (FS group, n=14)were injected with equal volume 0.9% sodium chloride, the rats of normal-control group(NC group, n=12) were placed in 37℃ water about 5 minutes, then injected with equal volume sodium chloride.Latency, duration and grade of FS were observed and compared;step down test and step through test were used to detect short-term learning and memory ability;HE staining was adopted to observe the changes of histopathology in hippocampal neuron; Timm staining was used to observe mossy fiber sprouting (MFS) in hippocampus. Results 1)Seizure duration of NT group was shorter than that of FS group (P<0.05); seizure grade of NT group was significantly less than that of FS group (P<0.01);there was no significantly difference in seizure latency between two groups (P>0.05).2)Both step down test and step through test exhibited that the error times of FS group was at most, there were significant difference (P<0.01), but there were no significant difference (P>0.05) in NC group and NT group;after 24 hours, the step-down latency and step-though latency of FS group were obviously shorted, and had significant difference (P<0.05), there were also no significant difference (P>0.05) in NC group and NT group.3) HE staining showed that there were much lighter brain damage in NT group than in FS group.4) In FS-control group, Timm staining particle was significantly increased in the inner molecular layer of DG and stratum oriens of CA3 area, compared with NC group there had significant difference (P<0.01).Intervention with naloxone made it obviously decreased, compared with FS group significant difference could be seen(DG:P<0.01, CA3:P<0.05), but no significant difference compared with NC group (P>0.05). Conclusions Naloxone can lighten the brain damage resulted from repeated FS;Repeated FS can result in deficits of short-term learning and memory ability in rats, early intervention with naloxone can improve this recognition functional impairment;naloxone can degrade the degree of mossy fiber sprouting, this is one of possible neuromechanism of naloxone for improving cognitive dysfunction.
Key words
naloxone /
febrile seizures /
learning and memory /
mossy fiber sprouting
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