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<title>Abstract</title> The current study aimed to examine the neurobehavioral activity of<italic> Artemisia monosperma Delile </italic>(ARM) ethanolic extract in adult male rats. Phytochemicals was screened using GC˗MS and HPLC analysis. ARM’s acute oral toxicity was determined. The study included four equal groups (n=12): the 1<sup>st</sup> Control, the 2<sup>nd</sup> Diazepam (DIZ), the 3<sup>rd</sup> ARM-high group (ARM-H), and the 4<sup>th</sup> ARM-low group (ARM-L). The ARM extract effect on the CNS activity was evaluated via behavioral tests, brain neurotransmitters and <italic>GABA</italic><sub><italic>A</italic></sub><italic> </italic>receptors (<italic>GABARAP)</italic>. HPLC analysis revealed the presence of coffeic acid, rutin, gallic acid, and querectin. In the open field test (OFT), ARM significantly <italic>(p < 0.001) </italic>decreased immobility time and line crossings. ARM significantly <italic>(p < 0.05)</italic> increased the brain γ-aminobutyric acid (GABA). ARM significantly <italic>(p < 0.05)</italic> up-regulated the brain mRNA expression levels of <italic>GABARAP</italic> and <italic>BDNF</italic>, meanwhile, <italic>MAOA</italic> levels were significantly <italic>(p < 0.05)</italic> downregulated. For the first time, <italic>A. monosperma</italic> ethanolic extract might keep CNS depressant and antioxidative effects which could be attributable to its phytochemicals. Further toxicological and pharmacological studies are required for the semi-purified phytochemicals.
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DOI: 10.21203/rs.3.rs-5338696/v2
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