Abstract
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.
Original language | English |
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Pages (from-to) | 760-767 |
Number of pages | 8 |
Journal | European Neuropsychopharmacology |
Volume | 23 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2013 |
Bibliographical note
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.
Keywords
- 5-HT receptor
- CB2 receptors
- Cannabinoids
- Marijuana
- Receptor internalization
- Serotonin
- Β-Arrestins
ASJC Scopus subject areas
- Pharmacology
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
- Pharmacology (medical)