| BackgroundOlanzapine is an atypical antipsychotic drug that improves the function of various neurotransmitters. Compared with other atypical antipsychotics, it is less likely to cause side effects, with a high security and a low risk of extra-pyramidal side-effects, and becomes the first-line drugs to treat schizophrenia and other mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptor (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Hypothalamic arcuate nucleus that lies in the hypothalamus nodule compartment week belt participates in the regulation of pituitary function, food intake, the autonomic nervous activity, analgesia, endocrine, and other physiological activities.ObjectiveTaken adult female SD rats as the research objects, this study by giving the drug intervention to discusses the effect of Olanzapine on the body weight of rats, the effect of arcuate nucleus discharge and the mechanism of H1 receptor in this role.Methods1.Forty-eight female SD rats were randomly divided into two groups, the control group(n=12) and the model group(n=36). After 1 week high calorie diet of food. Model group were randomly divided into three groups (n=12):olanzapine group, betahistine group and olanzapine+betahistine group.2.Given 2 weeks drug intervention, O group were given gavaged the olanzapine 1mg/Kg a day, B group were given gavaged the betahistine 1mg/Kg a day, O+B group were given gavaged the same dose of the nitrogen and betahistine, no intervention of the control group.3.Recorded the daily food intake and weight gain of the rats.4.The open-field test were used to evaluate behaviors of the rats, Immunohistochemistry was used to detect the histamine H1 receptors receptor protein expression in arcuate nucleus neurons of all groups. Prepared containing the arcuate nucleus of the hypothalamus in vitro brain slices, extra-cellular recording method was used to record the discharge of arcuate nucleus neurons.Results1.The rats of O group has a significantly in food intake and weight gain, the weight of O+B treatment group is between the O group and the normal group, the weight of the three groups have significant differences, there were no significant differences between the normal group and B group.2.The Open-files Text shows:there were no significant differences between the normal group and B group. This experimental results prove that this experiment used dose achieve the clinical effective concentration. There were no significant differences between the normal group and B group.3.Electron microscope results:The O group arcuate nucleus neurons discharge frequency and magnitude was higher than the control group, and O+B group and B group, the B group was lower than the control group.4.Immunohistochemical results:There were significant differences between the O group and B treatment group and normal group about the expression of the histamine H1 receptor in the hypothalamic arcuate nucleus neurons. There were no significant differences between the normal group and O+B group.Conclusionsl.Olanzapine could increase the rat food intake and body weight. Olanzapine could increase the discharge of hypothalamic arcuate nucleus neurons in the rat, which related of the histaminergic H1 receptor pathway.2.The results of Betahistine part block Olanzapine in food intake and body weight of rats and the discharge of hypothalamic arcuate nucleus neurons:Histaminergic H1 receptor pathway was one of the pathways that Olanzapine excited arcuate nucleus neurons. |
