RGD Reference Report - Neuroprotective effects of HTR1A antagonist WAY-100635 on scopolamine-induced delirium in rats and underlying molecular mechanisms. - Rat Genome Database

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Neuroprotective effects of HTR1A antagonist WAY-100635 on scopolamine-induced delirium in rats and underlying molecular mechanisms.

Authors: Qiu, Yimin  Chen, Dongmei  Huang, Xiaojing  Huang, Lina  Tang, Liang  Jiang, Jihong  Chen, Lianhua  Li, Shitong 
Citation: Qiu Y, etal., BMC Neurosci. 2016 Oct 19;17(1):66. doi: 10.1186/s12868-016-0300-9.
RGD ID: 405850209
Pubmed: PMID:27760517   (View Abstract at PubMed)
PMCID: PMC5070354   (View Article at PubMed Central)
DOI: DOI:10.1186/s12868-016-0300-9   (Journal Full-text)


BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR1AHumansubacute delirium  ISOHtr1a (Rattus norvegicus)mRNA more ...RGD 
Htr1aRatsubacute delirium  IEP mRNA more ...RGD 
Htr1aMousesubacute delirium  ISOHtr1a (Rattus norvegicus)mRNA more ...RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR1AHumanscopolamine increases expression ISOHtr1a (Rattus norvegicus)Scopolamine increases expression of Htr1a mRNA in amygdala more ...RGD 
Htr1aRatscopolamine increases expression EXP Scopolamine increases expression of Htr1a mRNA in amygdala more ...RGD 
Htr1aMousescopolamine increases expression ISOHtr1a (Rattus norvegicus)Scopolamine increases expression of Htr1a mRNA in amygdala more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr1a  (5-hydroxytryptamine receptor 1A)

Genes (Mus musculus)
Htr1a  (5-hydroxytryptamine (serotonin) receptor 1A)

Genes (Homo sapiens)
HTR1A  (5-hydroxytryptamine receptor 1A)


Additional Information