Khisti R T, Mandhane S N, Chopde C T
Department of Pharmaceutical Sciences, Nagpur University Campus, India.
Indian J Exp Biol. 1997 Dec;35(12):1297-301.
Incidence of severe depression is very common in Parkinson's disease (PD). Use of antidepressants in such cases is known to improve or worsen the existing PD. However, prediction of the effect of antidepressant on symptoms of PD is limited due to lack of suitable animal model. The present study examines the possibility of using haloperidol-induced catalepsy model in rats for this purpose. Antidepressants showed distinct effect on haloperidol-induced catalepsy, although most of them reduced forced-swimming induced immobility. In general, antidepressants with greater noradrenergic reuptake inhibition (desipramine, imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced, whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine) increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant, and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol-induced catalepsy. The results suggest that haloperidol-induced catalepsy model in rats needs to be incorporated in the screening procedure when evaluating the utility of antidepressant drugs for the treatment of depression associated with PD.
重度抑郁症在帕金森病(PD)中非常常见。已知在此类情况下使用抗抑郁药会改善或加重现有的帕金森病。然而,由于缺乏合适的动物模型,对抗抑郁药对帕金森病症状影响的预测有限。本研究探讨了为此目的使用氟哌啶醇诱导的大鼠僵住症模型的可能性。抗抑郁药对氟哌啶醇诱导的僵住症显示出不同的作用,尽管它们中的大多数减少了强迫游泳诱导的不动。一般来说,具有更强去甲肾上腺素再摄取抑制作用的抗抑郁药(地昔帕明、丙咪嗪、阿米替林、去甲替林、普罗替林和马普替林)会减轻氟哌啶醇诱导的僵住症,而具有5-羟色胺再摄取抑制作用的抗抑郁药(氟西汀和氯米帕明)则会加重氟哌啶醇诱导的僵住症。米安色林(一种非典型抗抑郁药)和阿普唑仑(一种苯二氮䓬受体类似物)对氟哌啶醇诱导的僵住症没有影响。结果表明,在评估抗抑郁药治疗与帕金森病相关抑郁症的效用时,大鼠氟哌啶醇诱导的僵住症模型需要纳入筛选程序。