Document Detail


Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT(2A)) receptor activity via ERK1/2 signaling.
MedLine Citation:
PMID:  23151877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jade M Franklin; Gonzalo A Carrasco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-08
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  67     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-06-28     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  145-59     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cannabinoid Receptor Agonists / pharmacology*
Cyclohexanols / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism*
MAP Kinase Signaling System / drug effects*
Male
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
RNA, Messenger / biosynthesis
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  genetics,  metabolism
Receptor, Cannabinoid, CB2 / antagonists & inhibitors,  genetics,  metabolism
Receptor, Serotonin, 5-HT2A / genetics,  metabolism*
Transcription, Genetic / drug effects
Up-Regulation
Grant Support
ID/Acronym/Agency:
DA024329/DA/NIDA NIH HHS; R03 DA024329/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Cannabinoid Receptor Agonists; 0/Cyclohexanols; 0/RNA, Messenger; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 0/Receptor, Serotonin, 5-HT2A; 83003-12-7/3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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