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Neurosci Lett. 2013 Aug 26;548:165-9. doi: 10.1016/j.neulet.2013.05.039. Epub 2013 May 27.

Cannabinoid-induced upregulation of serotonin 2A receptors in the hypothalamic paraventricular nucleus and anxiety-like behaviors in rats.

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Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, 1251 Wescoe Hall Drive, 3048B Malott Hall, Lawrence, KS 66045, USA.


Recent behavioral reports suggest that repeated exposure to cannabis and synthetic cannabinoid agonists is linked with mental disorders associated with dysfunction of serotonin 2A (5-HT2A) receptor neurotransmission such as anxiety and depression. Here, we studied the effect of a nonselective cannabinoid agonist, CP55940, on the activity of 5-HT2A receptors in hypothalamic paraventricular nucleus (PVN). We detected that repeated exposure to CP55940 enhanced the prolactin and corticosterone neuroendocrine responses mediated by 5-HT2A receptors and increased the membrane-associated levels of 5-HT2A receptors in PVN. Importantly, we also detected increased anxiety-like behaviors in CP55940 treated rats compared to controls. The data presented here suggest that the mechanisms mediating the cannabinoid-induced upregulation of 5-HT2A receptors would be brain-region specific, as we were unable to detect a CP55940-induced upregulation of 5-HT2A mRNA. Our results might provide insight into the molecular mechanism by which repeated exposure to cannabinoids could be associated with the pathophysiology of neuropsychiatric disorders.


(−) DOI; (−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol; 5-HT; 5-HT(2A); 5-HT(2A) receptor; 5-hydroxytryptamine; CP 55,940; ERK; G-proteins; Hypothalamus; Marijuana; PVN; Serotonin; [(−)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane HCl]; extracellular kinase; hypothalamic paraventricular nucleus; serotonin 2A; Δ(9)-THC; Δ(9)-tetrahydrocannabinol

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