Effects of(-)stepholidine in animal models for schizophrenia  

作　　者：Bart A ELLENBROEK Xue-xiang ZHANG Guo-zhang JIN 

机构地区：[1]Department of Cognitive Neurosciences, Section Molecular Neurobiology, University of Nijmegen, 6500 HB Nijmegen, The Netherlands [2]Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2006年第9期1111-1118,共8页中国药理学报（英文版）

基　　金：Project supported by the National Basic Research Program 973 from Ministry of Science and Technology in China(№2003CB515401)

摘　　要：Aim： （-）Stepholidine （SPD） is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D1 and a D2 antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia. Methods： The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated. Results： In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801- induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801. Conclusion： The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.Aim： （-）Stepholidine （SPD） is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D1 and a D2 antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia. Methods： The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated. Results： In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801- induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801. Conclusion： The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.

关 键 词：acoustic startle response ANTIPSYCHOTICS APOMORPHINE dopamine D-1 receptor dopamine D-2 receptor MK801 paw test prepulse inhibition CLOZAPINE HALOPERIDOL 

分 类 号：R749.3[医药卫生—神经病学与精神病学]