Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, United States; Department of Biomedical Engineering, State University at New York at Buffalo, Buffalo, NY, United States.
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, United States; Department of Psychology, State University at Buffalo, Buffalo, NY, United States.
Neurosci Lett. 2021 Jul 13;757:135976. doi: 10.1016/j.neulet.2021.135976. Epub 2021 May 21.
This study examined the effects of chronic treatment of the antipsychotic drugs, haloperidol and olanzapine, on microglial activation in the brain. In addition, we explored the interaction of these antipsychotic drugs with normal and high-fat diet. In order to measure activated microglial expression, we used [H] PK11195 in vitro autoradiography. Male Sprague Dawley rats were given a diet of either regular chow diet or a high-fat diet, and assigned either water, haloperidol drinking solution (1.5 mg/kg), or olanzapine drinking solution (10 mg/kg) for four weeks. Following treatment, rats were euthanized and brains extracted for [H] PK11195 autoradiography. Rats on 4 weeks of a high-fat diet showed increased [H] PK11195 binding compared to rats on a normal diet in the temporal association cortex (19 %), ectorhinal cortex (17 %), entorhinal cortex (18 %), and perirhinal cortex (18 %), irrespective of drug treatment. These are regions associated with memory, sensory, and visual processing. Rats treated with either haloperidol or olanzapine showed no differences in [H] PK11195 binding compared to the control group. However, there were differences between the 2 different antipsychotic medications themselves. Haloperidol increased [H] PK11195 binding in the amygdala (23 %), ectorhinal cortex (24 %), and perihinal cortex (29 %), compared to olanzapine. These results corroborate a known role of a high-fat diet and central inflammatory changes but suggest no role of these antipsychotic drugs in promoting neuroinflammation across 4 weeks compared to normal control rats.
这项研究考察了抗精神病药物氟哌啶醇和奥氮平的慢性治疗对大脑中小胶质细胞激活的影响。此外，我们还探索了这些抗精神病药物与正常饮食和高脂肪饮食的相互作用。为了测量激活的小胶质细胞表达，我们使用了 [H] PK11195 体外放射自显影。雄性 Sprague Dawley 大鼠给予常规饮食或高脂肪饮食，并给予水、氟哌啶醇饮用水溶液（1.5 mg/kg）或奥氮平饮用水溶液（10 mg/kg）治疗四周。治疗后，处死大鼠并提取大脑进行 [H] PK11195 放射自显影。与正常饮食组相比，高脂肪饮食组大鼠的颞联合皮层（19%）、外侧皮层（17%）、内嗅皮层（18%）和旁海马回皮层（18%）的 [H] PK11195 结合增加，而不论药物治疗如何。这些区域与记忆、感觉和视觉处理有关。与对照组相比，接受氟哌啶醇或奥氮平治疗的大鼠在 [H] PK11195 结合方面没有差异。然而，这两种不同的抗精神病药物本身存在差异。与奥氮平相比，氟哌啶醇增加了杏仁核（23%）、外侧皮层（24%）和旁海马回皮层（29%）的 [H] PK11195 结合。这些结果证实了高脂肪饮食和中枢炎症变化的已知作用，但与正常对照组大鼠相比，这些抗精神病药物在 4 周内没有促进神经炎症的作用。
