The experimental study about the effects of psychotropic drugs on the mechanism of water intoxication

精神分裂症患者的水中毒以病态多饮为特征，并引起意识障碍和抽搐等严重症状。抗精神病药物的治疗被认为是导致这种疾病的原因之一。虽然已经提出了水中毒的几种机制，但它们仍然不清楚。在这项研究中，我们研究了用十酸氟哌啶醇（HalomonthR; 10、20 mg/kg, ig）慢性治疗（8周）对大鼠视上核（SON）高渗刺激的精氨酸抗利尿素（AVP）释放和行为改变（水摄入和活动）的影响。1)高渗刺激后30 ~ 60 min（第三期）主要发生摄水。特别地，氟哌啶醇治疗动物的饮水率和饮水量显著增加。2)相同动物在高渗刺激后30 ~ 90 min AVP水平升高。3)氟哌啶醇组纹状体多巴胺水平明显低于对照组。我们证明，长期使用癸酸氟哌啶醇治疗可增强SON高渗刺激诱导的水摄入和AVP的释放。这些结果提示，慢性氟哌啶醇治疗引起的水摄入量和AVP水平的增加可能与AVP与SON多巴胺能系统的相互作用有关。

Water intoxication in Schizoprenic patient is characterized by morbid polydipsia and induces severe symptoms such as conscious disturbance and convulsions. And treatment with antipsychotics has been speculated as one of the causal factors in this disorder. Although several mechanisms responsible for development of water intoxication have been proposed, they are still unclear. In this study, we have undertaken to investigate the effect of chronic treatment (8 weeks) with haloperidol decanoate(HalomonthR ; 10, 20 mg/kg, i.m.) on arginine vasopressin (AVP) release and behavioral changes (water-intake and ambulation) by hyperosmotic stimulation of the supraoptic nucleus (SON) in rats.1) The incidence of water-intake mainly produced 30-60 min (third period) after hyperosmotic stimulation. In particular, there was a marked increase in the incidence and volume of water-intake in haloperidol treated animals.2) AVP levels were increased 30-90 min after hyperosmotic stimulation in the same animals.3) Dopamine levels in striatum in haloperidol treated animals were smaller than those in the control.We demonstrated that chronic treatment with haloperidol decanoate enhanced hyperosmotic stimulation-induced water-intake and release of AVP in SON. These results suggest that the increasing effect of water-intake and AVP levels caused by chronic haloperidol treatment may connect with interaction between AVP and dopaminergic system in SON.