Objectives: This study determined the chemical composition of essential oil obtained from fresh leaf of Plectranthus aegyptiacus, and evaluated it for novelty-induced behavioural (NIB) and determine its mechanism(s) of action in mice. Methods: The oil was hydro-distillated, and analyzed using gas chromatography-mass spectrometry. The effects of the oil (50, 100 and 150 mg/kg; i.p., n=6) on novelty-induced behavioural was assessed using open field test and head dipping on hole board. Probable mechanism(s) were evaluated using antagonists: flumazenil, naloxone and cyproheptadine at 2 mg/kg each, atropine and yohimbine at 5 mg/kg and 1 mg/kg respectively. Key Findings: The LD50 values obtained were 2154 and 490 mg/kg for oral and intraperitoneal routes respectively. The oil (50, 100 and150 mg/kg) significantly (p<0.05, 0.01 and 0.01) inhibited all NIB and head dips. Flumazenil significantly (p<0.05) reversed the effect of the oil on NIB; atropine, naloxone and cyproheptadine significantly (p<0.01, 0.01 and 0.001) potentiated inhibitory effect on NIB respectively, while yohimbine showed no significantly effect. The analyzed oil showed 61 compounds, and the major compounds were carvacrol, germacrene-D, p-cymene and [1,1'-Bicyclopentyl]-2,2'-diol. Conclusions: The study concluded that the oil possessed central nervous system depressant activity, which could be mediated mainly through augmentation of GABAergic neurotransmission, while cholinergic-(muscarinic), adrenergic and serotonergic pathways may be involved.
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