| Objective: Evaluation of cnidium monnieri hypnosis active component(CHC) hypnosis and promote the effect of learning and memory and hangover reaction and dependence and tolerance, tolerance mechanism are discussed.Method: 1. The CHC hypnotic effects and tolerability: mice, lavage CHC 520 mg/kg and 260 mg/kg and 130 mg/kg three doses, points 2 times, each time interval seven hours a day, 30 days in a row, ck and diazepam 6 mg/kg positive control, observation of CHC coordination hypnotic dose of sodium pentobarbital sleep latency, sleep duration. Using Morris water maze navigation and space exploration evaluation method for the test space cognition and memory in mice; Respectively to observe the CHC for2 days,8days,15 days,29days to sleep latency in mice, and the effect of sleep duration and 1 day,7days,14 days,28days on autonomic activities in mice, the influence of the evaluation of CHC tolerance; Testing for 30 days in mice hippocampal gamma-aminobutyric acid(gamma amino butyric acid, GABA) of GABAA receptor and coding P- glycoprotein(P- glycoprotein, Pgp) of MDR1 gene, from the level of gene expression to explore CHC not present tolerance mechanism.2. The CHC hangover response evaluation: mice, lavage CHC 520 mg/kg and 260 mg/kg and 130 mg/kg three doses, points 2 times, each time interval seven hours a day, two days in a row, ck and diazepam 6 mg/kg positive control, were observed before and after dosing CHC in 2 days to sleep of mice autonomic activity, avoid the influence of dark reflection, evaluation of CHC hangover.3. The CHC dependence evaluation: take rats, gastric CHC 260 mg/kg and 130 mg/kg and 65 mg/kg three doses, for eight weeks, since the start, after the treatment in the weekend to stop for 1 day per week, ck and diazepam 3 mg/kg positive control, observation CHC vertical tail, anger of rat, bite each other, nose, throat, ear, tooth fibrillation, drooping eyelids pale these withdrawal symptoms and the influence of body weight after withdrawal, evaluation, and the dependence of the CHC.Results:1. The CHC hypnotic effect in mice and tolerance response: 2 days, sleep incubation period, there was no significant difference between groups. Sleep duration, CHC high dose and middle dose group was significantly higher than that of the diazepam group(P<0.001, P<0.001), CHC hypnotic effect is remarkable. CHC space cognitive ability in mice, no significant effect. Diazepam can significantly shorten the target time and the proportion of total distance of target distance, diminished the spatial reference memory ability of mice, and CHC spatial reference memory there was no significant impact on the mice. Different time points to medicine mice sleep latency period there was no significant difference between the rate of change of each group; Sleep duration, sleep duration of mice diazepam decreased gradually, and other groups showed no significant downward trend; The activities in mice, the different groups of mice activity times the rate of change of time had no significant difference; Stand stand number in mice, the mice have lower trend, but in order to reduce the obvious degree of diazepam groups. CHC high, medium and low dose group of GABAA alpha 1 gene expression level was significantly higher than that of the diazepam group(P<0.05); GABAA- alpha 5 diazepam group is significantly higher than the level of gene expression in the blank control group(P<0.05), CHC dose and low dose group of GABAA- alpha 5 gene expression level was significantly lower than that of the diazepam group(P<0.05); MDR1 gene expression diazepam group of MDR1 gene expression level slightly higher than the blank control group and CHC each dosage group, but there was no significant difference between groups.2. The CHC hangover reaction in mice: the number of activities, and blank control group, high dose group of CHC, activity times and low dose group were significantly higher than before(P<0.001, P<0.05, P<0.01, P<0.05), and diazepam group there was no significant difference before and after sleep. The number of stand, and blank control group, the diazepam group, CHC woke up, high, medium and low dose group were significantly lower than before(P<0.01, P<0.01, P<0.001, P< 0.001, P<0.001). Suggest that CHC can significantly reduce the number of autonomic activities in mice, and the number of times to wake up activity inhibition below diazepam. Avoid dark incubation period, high dose of group and the blank control group, CHC CHC incubation period after come to low dose group were significantly higher than before(P<0.05, P<0.05, P<0.01), diazepam and CHC dose group compared with before there was no significant difference after waking. Wrong number, diazepam group had a significantly below the bed woke up wrong number(P<0.01), and other groups there was no significant difference compared with woke up before sleep. Show that CHC could significantly prolong the mice avoid dark incubation period, decrease The Times of dark error avoidance and the extension of incubation period of wake up dark the diazepam group significantly.3. The CHC dependence of rat response: observation of withdrawal symptoms, rely on the group of rats, 5 weeks after drug withdrawal vertical tail, 6 weeks when angered, bite each other, nose flow; At 7 weeks appear throat singing, ear pale; At 8 weeks, appear tooth fibrillation, drooping eyelids. CHC in high dose group was 7 weeks throat singing, CHC low dose group of throat singing in 8 weeks. Weight change, and diazepam group rats from drug withdrawal 16 h, weight loss, and CHC each dose group, there was no significant weight loss.Conclusion: CHC hypnotic effect significantly, and will not affect the ability of learning and memory in mice does not appear tolerability, hangover and dependency of these adverse reaction; Diazepam tolerance may cut, associated with GABAA alpha 1 down and GABAA alpha 5 and MDR1 raised, and CHC is not present these gene expression changes. |
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