title: Cannabinoid-induced upregulation of serotonin 2A receptors in the hypothalamic paraventricular nucleus and anxiety-like behaviors in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, 1251 Wescoe Hall Drive, 3048B Malott Hall, Lawrence, KS 66045, USA.
authors.forename: Jade M
authors.initials: JM
authors.lastname: Franklin
authors.forename: Matt
authors.initials: M
authors.lastname: Mathew
authors.forename: Gonzalo A
authors.initials: GA
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage; D002186:Cannabinoids / Q000378:metabolism*; D003511:Cyclohexanols / Q000008:administration & dosage*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D003511:Cyclohexanols; D044402:Receptor, Serotonin, 5-HT2A; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
keywords: (−) 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