Nassar Ahmad, Sharon-Granit Yael, Azab Abed N
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; School for Community Health Professions - Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Neurosci Lett. 2016 Jul 28;626:59-67. doi: 10.1016/j.neulet.2016.05.019. Epub 2016 May 12.
Recent evidence suggests that inflammation may contribute to the pathophysiology of mental disorders and that psychotropic drugs exert various effects on brain inflammation. The administration of bacterial endotoxin (lipopolysaccharide, LPS) to mammals is associated with robust production of inflammatory mediators and pathological changes in body temperature. The objective of the present study was to examine the effects of four different psychotropic drugs on LPS-induced hypothermia and production of prostaglandin (PG) E2, tumor necrosis factor (TNF)-α and phosphorylated-p65 (P-p65) levels in hypothalamus of LPS-treated rats. Rats were treated once daily with lithium (100mg/kg), carbamazepine (40mg/kg), haloperidol (2mg/kg), imipramine (20mg/kg) or vehicle (NaCl 0.9%) for 29 days. On day 29, rats were injected with LPS (1mg/kg) or saline. At 1.5h post LPS injection body temperature was measured, rats were sacrificed, blood was collected and their hypothalami were excised, homogenized and centrifuged. PGE2, TNF-α and nuclear P-p65 levels were determined by specific ELISA kits. We found that lithium, carbamazepine, haloperidol and imipramine significantly attenuated LPS-induced hypothermia, resembling the effect of classic anti-inflammatory drugs. Moreover, lithium, carbamazepine, haloperidol and imipramine differently but significantly affected the levels of PGE2, TNF-α and P-p65 in plasma and hypothalamus of LPS-treated rats. The results suggest that psychotropic drugs attenuate LPS-induced hypothermia by reducing hypothalamic production of inflammatory constituents, particularly PGE2. The effects of psychotropic drugs on brain inflammation may contribute to their therapeutic mechanism but also to their toxicological profile.
最近的证据表明，炎症可能在精神障碍的病理生理学中起作用，并且精神药物对脑部炎症有多种影响。给哺乳动物注射细菌内毒素（脂多糖，LPS）会导致炎症介质的大量产生和体温的病理变化。本研究的目的是检查四种不同的精神药物对LPS诱导的体温过低以及LPS处理的大鼠下丘脑前列腺素（PG）E2、肿瘤坏死因子（TNF）-α和磷酸化-p65（P-p65）水平的影响。大鼠每天用锂（100mg/kg）、卡马西平（40mg/kg）、氟哌啶醇（2mg/kg）、丙咪嗪（20mg/kg）或赋形剂（0.9%氯化钠）处理一次，共29天。在第29天，给大鼠注射LPS（1mg/kg）或生理盐水。在注射LPS后1.5小时测量体温，处死大鼠，采集血液，并切除其下丘脑，进行匀浆和离心。通过特定的ELISA试剂盒测定PGE2、TNF-α和核P-p65水平。我们发现，锂、卡马西平、氟哌啶醇和丙咪嗪显著减轻了LPS诱导的体温过低，类似于经典抗炎药物的效果。此外，锂、卡马西平、氟哌啶醇和丙咪嗪对LPS处理的大鼠血浆和下丘脑中PGE2、TNF-α和P-p65的水平有不同但显著的影响。结果表明，精神药物通过减少下丘脑炎症成分的产生，特别是PGE2，来减轻LPS诱导的体温过低。精神药物对脑部炎症的影响可能有助于其治疗机制，但也与其毒理学特征有关。
