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• W2790496684 abstract "Background and Purpose Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in G q ‐protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5‐HT 2A receptor, a G q ‐protein coupled receptor involved in lithium's actions. Experimental Approach 5‐HT 2A receptor function was assessed in mice by measuring the behavioural (head‐twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c‐fos, Egr2) responses to 5‐HT 2A receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5‐HT 2A receptor function. Because lithium and 5‐HT 2A receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co‐administration with the SSRI citalopram in microdialysis (extracellular 5‐HT) experiments. Key Results Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5‐HT 2A receptor agonist DOI. Repeated lithium also inhibited DOI‐evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L‐690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR‐A014418) did not. Finally, ebselen enhanced the increase in extracellular 5‐HT induced by citalopram, and also increased regional brain 5‐HT synthesis. Conclusions and Implications Our data demonstrated lithium‐mimetic effects of ebselen in different experimental models of 5‐HT 2A receptor function, probably mediated by IMPase inhibition. This evidence of lithium‐like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent." @default.
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• W2790496684 date "2018-05-22" @default.
• W2790496684 modified "2023-10-10" @default.
• W2790496684 title "Ebselen has lithium-like effects on central 5-HT_2A receptor function" @default.
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• W2790496684 doi "https://doi.org/10.1111/bph.14179" @default.
• W2790496684 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6003638" @default.
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