| BackgroudBlonanseri,an inhibitor of D2/5-HT2 receptor,manufactured by Dainippon Sumitomo,has a completely innovative chemical structure.As a antipsychotic drug clinically,it had been on sale in Japan,and manufactured and had been appeared on the market in our country last year.Blonanseri,belonged to antagonist of 5-HT and Dopa,is one of the second generation of novel antipsychotic drugs.It has the equivalent interruption effection on Dopamine D2 receptor compared with haloperidol,and a strong block effection on5-HT2 A.Compared with other antipsychotic drugs,Blonanseri has better selectivity on the two receptors.Compared with other antipsychotics,Blonanseri effectively alleviates schizophrenic’s disgnosia,and is less likely to cause extrapyramidal side effects compared with clinical used antipsychotics in Europe and the United States.However,although the drug instructions did not mention the side effect of weight gain,it appeared that Blonanseri had the weight gain in some persons in the treatment in Japan and III phase clinical trial in China.Nucleus arcuatus hypothalami,located surrounding the Hypothalamic area,participated in the role of hypophysis,has closely relation with regulation of physiologic function such as ingestion,autonomic nervous activity,analgesia,endocrine.We are through this experiment to verify that whether Blonanseri is increased rat diet and weight by the activity of dopamine D2 receptor neurons.ObjectiveTo investigate the role of Blonanseri on rat body weight and food ration,and whether the dopamine D2 receptor in the hypothalamus arcuate nucleus neurons take part in the process.Methods1.24 adult male SD rats were divided into experimental group and control group randomly.The rats in experimental group were treated by Blonanseri,0.1mg/Kg/d,two times interval 12 hours by intragastric administration.The rats in control group were treated by normal saline,in the same does and times of the experimental group.2.The daily food intake and weight gain of the rats was recorded in the to weeks after first intragastric administration.The sufficient food and water was supplied on the cage cover at 18:00 everyday;and the rest food was measured at 9:00 next day and the average daily food intake was got.Weigh the body weight at 9:00 everyday from the second day after treated until 2w+1 days,the first 1 day body weight gain is two adjacent weight difference.3.Extra-cellular recording method was used to record the discharge of arcuate nucleus neurons.To observe the effect of antagonist and agonist of dopamine D2 receptor on the discharge.4.Immunohistochemistry was used to detect protein expression of the dopamine D2 receptor in arcuate nucleus neurons of two groups.Results1.After 2weeks,the average daily intake was increased from17.47±2.83 g to23.33±3.21g/16.96±2.55 g to 32.57±3.35 g in control and experimental group respectively;the average daily intake in the experimental group was higher than the rats in control group from fifth day.After 2weeks,the weight gain was increased from1.72±1.72 g to11.33±4.32g/1.69±1.23 g to 23.48±7.62 g in control and experimental group respectively;the average daily intake in the experimental group was higher than the rats in control group from fourth day.2.The arcuate nucleus neurons discharge frequency and magnitude in experimental group was higher than the control group.Rraclopride,a the dopamine D2 antagonist,suppress the arcuate nucleus neurons discharge in two groups.However the suppressed effective was higher in experimental group.3.Immunohistochemistry showed that the expression of D2 dopamine receptor in hypothalamic arcuate nucleus neurons was increased after given Blonanseri byintragastric administration.ConclusionsBlonanse,a Dopamine D2 receptor antagonist,increased excitability and expression of Dopamine D2 receptor in hypothalamic arcuate nucleus neurons.The mechanism of body weight gain is probably by increased food intake through increased the excitability of neurons by inhibited dopamine D2 receptor activity in hypothalamic arcuate nucleus neurons... |
