Effects of low-dose trichlorfon on passive avoidance behavior in mice

Abstract : Objective To study the effects of low-dose trichlorfon (Dip) on passive avoidance behavior in different mice. Methods of normal and repeated cerebral ischemia-reperfusion model mice, using passive avoidance test and jumping test for behavioral testing. Results The dark test showed that Dip (2. 75211mg. kg21, ip, Bid × 7 days ) had a certain promoting effect on the behavior of normal mice ; the platform test showed (5 ~ 11mg. kg21, ip, Bid × 7 days) ) It has a significant improvement effect on the behavioral activities of mice after repeated cerebral ischemia and reperfusion. Conclusion Low-dose Dip can promote and improve the passive avoidance behavior of mice , and its mechanism may be related to the increase of acetylcholine content in the brain.

Key words : trichlorfon ; passive avoidance behavior ; repeated cerebral ischemia and reperfusion

Metrifonate (met rifonate, Met) is an acetylcholinesterase (Ach E) inhibitors, pharmacokinetic and pharmacodynamic show, Met useful for the treatment of Alzheimer's disease (AD) is. Dipterex (Dip) and Met are both organophosphorus compounds and are long-acting Ach E inhibitors , both of which can be converted to competitive irreversible Ach E inhibitor dichlorvos (DDvp) under non-enzymatic conditions. . In view of the toxicity of Dip , we used ultra-small doses of trichlorfon and observed its behavioral activities in different mice.

influences.

Object and method

1. Material : Trichlorfon Hubei Province Shalongda Co., Ltd. products ; Kunming mice , provided by the Anyang Medical Laboratory Animal Center ( 皖医实动准 01 号 ); Jumping platform, dark detector by Zhejiang Ninghai Baishi drug test The sound 2 light 2 electric one-way shuttle box produced by the instrument factory was modified.

Second, the dark test

Normal 2 months old mice were administered with ip , Bid × 7 days , and the darkness test was performed according to the literature 1 h after the last administration .

3. Mouse cerebral ischemia-reperfusion model mice were administered ip , Bid × 7 days , and repeated cerebral ischemia according to the literature 1 h after the last administration .

Fourth, the platform test

The use of repeated cerebral ischemia-reperfusion model mice, according to the literature estimates.

V. Statistical processing methods The experimental data are expressed as x ± s , and the inter-group t- test.

Result

First, the impact on the body weight of mice packet Dip in Table 1, groups of mice 12 saline, body weight before the test (18 5 ± 3 98.. ) G; Dip each group were 49, before the experiment body weight (19 . 3 ± 3 . 13)g . Body weight was measured one week later , and the saline group was (26.3 ± 1.64) g . The percentage of weight gain was 30%, and there was a statistically significant difference between the before and after comparisons (P < 0.01). The Dip group was ( 21.6 ± 2.59) g, and the percentage of weight gain was 11%. There was no statistically significant difference between the two groups. ( P > 0 . 05) .

Second, the Dip avoidance test in mice as shown in Table 1, training Dip2. 75, 5. 5 and 11mg. Kg21 significantly shortened the escape latency of mice, 2. 75mg. Kg21 can significantly reduce the number of errors. During the test, each group of Dip can significantly reduce the number of errors in the mice , and there is no significant difference in the incubation period.

The effect of Dip on the platform test of repeated cerebral ischemia-reperfusion in mice compared with the NS group , the escaping latency of the sham operation group was significantly shortened , and the latency of the platform was significantly prolonged ; Dip5. 5 and 11 mg. kg21 significantly shortened the escape latency , 5. 5 mg. . kg21

Significantly extend the latency of the platform.

Discuss

Dip is attributed to organophosphates and is a persistent anti- Ach E drug that increases the amount of acetylcholine (Ach) in the body and brain . The results of this study showed that low dose Dip ( 2.77 ~ 11mg. kg21, ip) can shorten the EL and error times of mice in the dark test, indicating that it can promote the behavior of normal mice. Repeated cerebral ischemia-reperfusion can significantly impair the behavior of mice , and the mechanism of injury is very complicated. Studies have shown that repeated cerebral ischemia and reperfusion pathological changes similar animal AD, cerebral ischemia

It can damage the blood brain cholinergic, so reducing the content of Ach. The results of this study show that Dip (5. 5 ~ 11mg. kg21), ip) can shorten the EL of cerebral ischemia mice and prolong its SDL, indicating that Dip may improve the jumping platform of cerebral ischemia mice by increasing the amount of Ach in the brain. Test indicators. The study also showed that low-dose Dip can inhibit the increase of body weight while improving the behavior of mice , indicating that it still has some toxicity. Although toxicity, as nootropics for clinical wrong, but the results of this study have certain significance to find and develop new drugs to improve cognitive activity.

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