利培酮对谷氨酸功能低下的精神分裂症小鼠模型的作用

Effects of risperidone on the hypoglutamatergic schizophrenia model in mice

目的 观察第二代抗精神病药利培酮对地卓西平马来酸盐（MK-801）所致谷氨酸功能低下精神分裂症小鼠模型的作用。方法 昆明种雄性小鼠122只。（1）取32只小鼠，分为溶媒（腹腔注射溶媒）和不同剂量利培酮（腹腔注射0．025，0．050，0．075mg／kg）4组，每组8只，观察利培酮对小鼠探究行为和自主活动的影响。（2）取50只小鼠分为5组，每组10只，分别为空白对照组（溶媒＋溶媒）、MK-801模型组（腹腔注射溶媒＋MK-801 0．25mg／kg）和3个不同剂量的利培酮（方法同前）组（3组均含0．25mg／kg的MK-801），观察利培酮对MK-801致小鼠自主活动增加的影响。（3）取40只小鼠分为5组，每组8只。给药方案同前，观察利培酮对MK-801引起的刻板行为的影响。结果 （1）与溶媒组比较，利培酮剂量为0．050mg／kg和0．075mg／kg时，小鼠的探究行为和自主活动总路程减少（均P〈0．05和（0．001）；但低剂量（0．025mg／kg）对小鼠的探究行为（P=0．093）和自主活动（P=0．263）的影响未达统计学意义。（2）利培酮（0．025-0．075mg／kg）呈剂量依赖性地抑制由MK801引起的自主活动增加和刻板行为（均P〈0．05）。结论 利培酮能特异性地抑制MK-801引起的行为改变。

Objective To investigate the effects of risperidone on MK-801-indueed hypoglutamatergic schizophrenia model in mice. Methods （ 1 ） To investigate the effects of rispefidone on explorative behavior and spontaneous activity, mice were administered with risperidone （0. 025 mg/kg, 0. 050 mg/kg and 0. 075 mg,/kg） or vehicle 30 min before the test. Locomotor activity was recorded for 30 min with an automated video tracking system, in which the components of the locomotor activity counting were divided into exploration （the first 10 min） and spontaneous activity （the second 20 min）. （2） To evaluate the effects of risperidone on MK-801-induced hyperlocomotion and stereotyped behavior, mice were administered with risperidone （0.025 mg,/kg, 0.050 mg/kg and 0.075 mg/kg, i.p. ） or vehicle 5 min before administration of MK-801 （0. 25 mg/kg, i. p. ）. After the second injection, locomotor activity was recorded for 90 min by the video tracking system; stereotyped behavior was evaluated for 90 min using a ranked intensity scale by two raters who were blind to the drug treatment. Results Risperidone （0. 050 mg/kg and 0. 075 mg/kg） significantly inhibited the explorative behavior and spontaneous activity （P 〈 0. 05 and P 〈 0. 01, respectively）. Risperidone at 0. 025 mg/kg did not affect exploration （ P = 0. 093 ） and spontaneous activity （P = 0. 263）. Risperidone （0. 025-0. 075 mg/kg） dose-dependently antagonized MK- 801-induced hyperlocomotion and stereotypy. Conclusion Risperidone has a specific inhibition effect on MK-801-induced behavioral changes which may be involved with the pharmacological mechanism of risperidone on modulating dopamine, serotonin, and other neurotransmitters.