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• W2046753944 endingPage "159" @default.
• W2046753944 startingPage "145" @default.
• W2046753944 abstract "Abstract Recent behavioral studies suggest that nonselective agonists of cannabinoid receptors may regulate serotonin 2A (5‐HT 2A ) receptor neurotransmission. Two cannabinoids receptors are found in brain, CB1 and CB2 receptors, but the molecular mechanism by which cannabinoid receptors would regulate 5‐HT 2A receptor neurotransmission remains unknown. Interestingly, we have recently found that certain cannabinoid receptor agonists can specifically upregulate 5‐HT 2A receptors. Here, we present experimental evidence that rats treated with a nonselective cannabinoid receptor agonist (CP 55,940, 50 µg/kg, 7 days) showed increases in 5‐HT 2A receptor protein levels, 5‐HT 2A receptor mRNA levels, and 5‐HT 2A receptor‐mediated phospholipase C beta (PLCβ) activity in prefrontal cortex (PFCx). Similar effects were found in neuronal cultured cells treated with CP 55,940 but these effects were prevented by selective CB2, but not selective CB1, receptor antagonists. CB2 receptors couple to the extracellular kinase (ERK) signaling pathway by Gα i/o class of G‐proteins. Noteworthy, GP 1a (selective CB2 receptor agonist) produced a strong upregulation of 5‐HT 2A receptor mRNA and protein, an effect that was prevented by selective CB2 receptor antagonists and by an ERK1/2 inhibitor, PD 198306. In summary, our results identified a strong cannabinoid‐induced upregulation of 5‐HT 2A receptor signaling in rat PFCx. Our cultured cell studies suggest that selective CB2 receptor agonists upregulate 5‐HT 2A receptor signaling by activation of the ERK1/2 signaling pathway. Activity of cortical 5‐HT 2A receptors has been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results may provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to the pathophysiology of some cognitive and mood disorders in humans. Synapse, 2013. © 2012 Wiley Periodicals, Inc." @default.
• W2046753944 created "2016-06-24" @default.
• W2046753944 creator A5003555403 @default.
• W2046753944 creator A5064441760 @default.
• W2046753944 date "2012-12-08" @default.
• W2046753944 modified "2023-10-15" @default.
• W2046753944 title "Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT_2A) receptor activity via ERK1/2 signaling" @default.
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• W2046753944 doi "https://doi.org/10.1002/syn.21626" @default.
• W2046753944 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3552103" @default.
• W2046753944 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23151877" @default.
• W2046753944 hasPublicationYear "2012" @default.
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