Zis A P, Fibiger H C
Psychopharmacologia. 1975 Jul 23;43(1):63-8. doi: 10.1007/BF00437616.
The role of central dopaminergic mechanisms in the regulation of food and water intake was assessed by examining the effects of haloperidol and pimozide on various measures of feeding and drinking in rats. Haloperidol (0.20 mg/kg) or pimozide (0.45 mg/kg) did not significantly affect 1-hr water intake in response to 24 hrs of water deprivation, nor did they influence 2-hr food intake after 24 hrs food deprivation. However both pimozide and haloperidol significantly reduced drinking in response to injections of hypertonic saline. In addition, animals pretreated with these drugs drank less than controls in the absence of food (a measure of "non-prandial" drinking), and drank less than controls when the water was adulterated with quinine (a measure of "finickiness"). These drugs also significantly reduced food intake in response to injections of insulin and attenuated amphetamine anorexia. These deficits are similar to those observed after electrolytic lesions of the lateral hypothalamus or after 6-hydroxydopamine lesions of the substantia nigra. Because haloperidol and pimozide block central dopaminergic receptor sites, the present findings are consistent with the hypothesis that part of the lateral hypothalamic syndrome is the result of damage to the dopaminergic nigro-neostriatal projection. Finally, the data suggest that the changes in feeding and drinking induced by haloperidol and pimozide reflect genuine homeostatic deficits rather than being due to a neuroleptic-induced motor dysfunction.
通过研究氟哌啶醇和匹莫齐特对大鼠各种摄食和饮水指标的影响,评估了中枢多巴胺能机制在调节食物和水摄入中的作用。氟哌啶醇(0.20毫克/千克)或匹莫齐特(0.45毫克/千克)对24小时禁水后1小时的水摄入量没有显著影响,对24小时禁食后2小时的食物摄入量也没有影响。然而,匹莫齐特和氟哌啶醇都能显著减少高渗盐水注射引起的饮水。此外,用这些药物预处理的动物在无食物时(一种“非餐时”饮水的指标)比对照组饮水少,在水中加入奎宁时(一种“挑食”的指标)也比对照组饮水少。这些药物还能显著减少胰岛素注射引起的食物摄入量,并减轻苯丙胺性厌食。这些缺陷与下丘脑外侧电解损伤或黑质6-羟基多巴胺损伤后观察到的缺陷相似。由于氟哌啶醇和匹莫齐特阻断中枢多巴胺能受体位点,目前的研究结果与以下假设一致,即部分下丘脑外侧综合征是多巴胺能黑质-新纹状体投射受损的结果。最后,数据表明氟哌啶醇和匹莫齐特引起的摄食和饮水变化反映了真正的内稳态缺陷,而不是由于抗精神病药物引起的运动功能障碍。