TY - JOUR
T1 - Cannabinoid 2 receptor- and beta Arrestin 2-dependent upregulation of serotonin 2A receptors
AU - Franklin, J. M.
AU - Vasiljevik, T.
AU - Prisinzano, T. E.
AU - Carrasco, G. A.
N1 - Funding Information:
Funding for this study was provided by National Institute of Health/National Institute on Drug Abuse DA024329 and University of Kansas Startup Funds; neither NIDA nor University of Kansas had a further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2013/7
Y1 - 2013/7
N2 - Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP55,940) or selective CB2 receptor agonists (JWH133 or GP1a) upregulate 5-HT2A receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A receptors was prevented in cells stably transfected with either CB2 or Β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT2A receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT2A receptors by a mechanism that requires CB2 receptors and Β-Arrestin 2 in cells that express both CB2 and 5-HT2A receptors. 5-HT2A receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.
AB - Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP55,940) or selective CB2 receptor agonists (JWH133 or GP1a) upregulate 5-HT2A receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A receptors was prevented in cells stably transfected with either CB2 or Β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT2A receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT2A receptors by a mechanism that requires CB2 receptors and Β-Arrestin 2 in cells that express both CB2 and 5-HT2A receptors. 5-HT2A receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.
UR - http://www.scopus.com/inward/record.url?scp=84878821415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878821415&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2012.06.012
DO - 10.1016/j.euroneuro.2012.06.012
M3 - Article
C2 - 22841827
AN - SCOPUS:84878821415
SN - 0924-977X
VL - 23
SP - 760
EP - 767
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 7
ER -