Effect of intragastric administration of diphenoxylate on epileptic seizures and neurobehavioral changes in mice
10.3760/cma.j.cn371468-20230222-00083
- VernacularTitle:地芬诺酯灌胃对小鼠癫痫发作及神经行为的影响
- Author:
Jiaqi MA
1
;
Yue ZHANG
;
Xiaopeng QU
;
Chao WANG
;
Bei LIU
Author Information
1. 西安医学院，西安 710068
- Keywords:
Epilepsy;
Diphenoxylate;
Electroencephalogram;
Behavioral testing;
Nissl staining;
Mice
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2023;32(10):865-870
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of intragastric administration of diphenoxylate on inducing epilepsy in mice, as well as the changes in neurobehavioral and hippocampal neurons in mice.Methods:Forty C57 male mice aged 2-3 weeks were selected and divided into control group and diphenoxylate group using random number table method, with 20 mice in each group. The mice in the diphenoxylate group were given diphenoxylate (200 mg/kg) by gavage once a day for 14 consecutive days, while the control group mice were given an equal volume of 0.9% sodium chloride solution every day. After each gavage, the seizure status of mice within 2 hours was observed and the mice were graded based on the Racine score. Open field test, elevated cross test, and Morris water maze test were used to observe the neurobehavioral activities of mouse.A digital electroencephalogram machine was used to monitor the epileptic seizures of mice induced by diphenoxylate.Nissl staining was used to observe the damage of hippocampal neurons in mice.SPSS 25.0 software was used for statistical analysis of the data, and independent sample t-test was used for pairwise comparison. Results:The Racine grading results showed that the mice in diphenoxylate group exhibited grade 2 and 3 seizures at 1 hour after gavage. The EEG monitoring results showed that compared with before gavage, the frequency and amplitude of brain waves of mice in diphenoxylate group increased.In the open field test, the residence time in the central region of mice in diphenoxylate group was significantly lower than that of the control group ((12.21±3.37)s, (17.05±4.34)s, t=3.29, P<0.01). In the elevated cross test, the residence time in the open arm of mice in diphenoxylate group was significantly lower than that of the control group ((17.36±5.41)s, (26.70±9.06)s, t=3.31, P<0.01). In the Morris water maze test, the residence time in the platform quadrant of diphenoxylate group was significantly lower than that of the control group((22.08±6.76)s, (27.64±4.60)s, t=2.54, P<0.05). The residence time and the number of stays in the platform area of diphenoxylate group were both significantly lower than those of the control group(both P<0.05). Nissl staining showed that the number of hippocampal neurons in the CA3 region of mice treated with diphenoxylate was significantly lower than that in the control group((135.67±4.59), (140.67±2.73), P<0.05). Conclusion:Excessive diphenoxylate can induce seizures in mice, and the mice exhibit increased anxiety-like behavior and decreased spatial learning and memory abilities.
