title: Neuroprotective effects of HTR1A antagonist WAY-100635 on scopolamine-induced delirium in rats and underlying molecular mechanisms.
abstract: Limited surveys have assessed the performance of 5-hydroxytreptamine receptor 1A and its antagonist WAY-100635 in pharmacological manipulations targeting delirium therapies. The purpose of this paper was to assess the central pharmacological activity of WAY-100635 in a rat model of scopolamine-induced delirium and its underlying mechanism.
  
  
  
  A delirium rat model was established by intraperitoneal injection of scopolamine and behavioral changes evaluated through open field and elevated plus maze experiments. Concentrations of monoamines in the hippocampus and amygdalae were detected by high performance liquid chromatography. The effect of WAY-100635 on the recovery of rats from delirium was assessed by stereotactic injection of WAY-100635 and its mechanism of action determined by measuring mRNA and protein expression via real time PCR and western blotting methods. The total distance and the number of crossing and rearing in the elevated plus maze test and the time spent in the light compartment in the dark/light test of scopolamine-treated rats were significantly increased while the percentage of time spent in the open arms was decreased, showing the validity of the established delirium rat model. The measurement of the concentrations of noradrenaline, 3,4-dihydroxyphenylacetic acid, the homovanillic acid, 5-hydroxy-3-indoleacetic acid and serotonin concentrations in the cerebrospinal fluid (CSF) of scopolamine-induced delirium rats were significantly increased. The intra-hippocampus and intra-BLA injections of WAY-100635 improved the delirium-like behavior of rats by significantly reducing the expression of NLRP3 inflammasome and the release of IL1-β and IL8 into CSF.
  
  
  
  Taken together, these findings indicate that WAY-100635 may exert a therapeutic effect on post-operative delirium by controlling neurotransmission as well as suppressing neuroinflammation in the central nervous system.
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong University, 800 Dongchuan Rd., Minhang District, Shanghai, 200080, China. qiuqiumin2016@163.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong University, 800 Dongchuan Rd., Minhang District, Shanghai, 200080, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pain Management, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong University, 800 Dongchuan Rd., Minhang District, Shanghai, 200080, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong University, 800 Dongchuan Rd., Minhang District, Shanghai, 200080, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Pain Management, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong University, 800 Dongchuan Rd., Minhang District, Shanghai, 200080, China.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology and Pain Management, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shitong
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003693:Delirium / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012601:Scopolamine; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D015306:Biogenic Monoamines; D016207:Cytokines; D018696:Neuroprotective Agents; D010879:Piperazines; D011725:Pyridines; D012333:RNA, Messenger; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D012601:Scopolamine
keywords: Amygdala; Delirium; HTR1A antagonist; Hippocampus; Neuroinflammation; Neurotransmitter