Lin En-Ju D, Lee Nicola J, Slack Katy, Karl Tim, Duffy Liesl, O'brien Elizabeth, Matsumoto Izuru, Dedova Irina, Herzog Herbert, Sainsbury Amanda
Neuroscience Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Neuropharmacology. 2006 Dec;51(7-8):1129-36. doi: 10.1016/j.neuropharm.2006.07.006. Epub 2006 Aug 21.
Antipsychotic drugs have been used effectively for the treatment of schizophrenia symptoms, but they are often associated with metabolic side effects such as weight gain and endocrine disruptions. To investigate the possible mechanisms of antipsychotic-induced metabolic effects, we studied the impact of chronic administration of a typical antipsychotic drug (haloperidol) and an atypical antipsychotic (risperidone) to male rats on food intake, body weight, adiposity, and the circulating concentrations of hormones and metabolites that can influence energy homeostasis. Chronic (28days) haloperidol administration had no effect on food intake, weight gain or adiposity in male rats, whereas risperidone treatment resulted in a transient reduction in food intake and significantly reduced body weight gain compared to vehicle-treated control rats. Whereas neither antipsychotic had any effect on serum lipid profiles, glucose tolerance or the circulating concentrations of hormones controlled by the hypothalamo-pituitary-thyroid (free T4), -adrenal (corticosterone), -somatotropic (IGF-1), or -gonadotropic axes (testosterone), haloperidol increased circulating insulin levels and risperidone increased serum glucagon levels. This finding suggests that haloperidol or risperidone induce distinct metabolic effects. Since metabolic disorders such as obesity and type 2 diabetes mellitus represent serious health issues, understanding antipsychotic-induced endocrine and metabolic effects may ultimately allow better control of these side effects.
抗精神病药物已被有效地用于治疗精神分裂症症状，但它们常常与体重增加和内分泌紊乱等代谢副作用相关联。为了研究抗精神病药物诱发代谢效应的可能机制，我们研究了对雄性大鼠长期给予一种典型抗精神病药物（氟哌啶醇）和一种非典型抗精神病药物（利培酮）对食物摄入量、体重、肥胖程度以及可能影响能量平衡的激素和代谢物循环浓度的影响。长期（28天）给予氟哌啶醇对雄性大鼠的食物摄入量、体重增加或肥胖程度没有影响，而与给予赋形剂的对照大鼠相比，利培酮治疗导致食物摄入量短暂减少且体重增加显著降低。虽然两种抗精神病药物对血清脂质谱、葡萄糖耐量或由下丘脑 - 垂体 - 甲状腺轴（游离T4）、 - 肾上腺轴（皮质酮）、 - 生长激素轴（IGF - 1）或 - 促性腺轴（睾酮）控制的激素循环浓度均无任何影响，但氟哌啶醇可提高循环胰岛素水平，利培酮可提高血清胰高血糖素水平。这一发现表明氟哌啶醇或利培酮会诱发不同的代谢效应。由于肥胖和2型糖尿病等代谢紊乱代表着严重的健康问题，了解抗精神病药物诱发的内分泌和代谢效应最终可能有助于更好地控制这些副作用。
