Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress
| Autor: | María Salud García-Gutiérrez, Jorge Manzanares, Adrián Viudez-Martínez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Restraint Physical Hypothalamo-Hypophyseal System medicine.medical_specialty medicine.drug_class Hypothalamus Pituitary-Adrenal System Biology Hippocampus Anxiolytic Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Gene expression medicine Animals Cannabidiol Pharmacology (medical) Gene Pharmacology Dose-Response Relationship Drug Amygdala 030227 psychiatry Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Endocrinology Real-time polymerase chain reaction Gene Expression Regulation Receptor Serotonin 5-HT1A Restraint stress Stress Psychological 030217 neurology & neurosurgery medicine.drug |
| Popis: | [Background]: Research interest has grown around the potential therapeutic use of cannabidiol in mood-related disorders, due to its anxiolytic and antidepressant-like effects. These have been partially attributed to its action as an allosteric modulator of 5-HTR1A. However, the exact mechanism supporting cannabidiol properties remains unclear. [Aims]: To assess the effects of cannabidiol on different targets of the hypothalamus-pituitary-adrenal axis under baseline and stress conditions. [Methods]: We administered cannabidiol (5 mg/kg, 15 mg/kg or 30 mg/kg, intraperitoneally) or vehicle to male C57BL/6J mice 90 min before single restraint stress exposure (20 min). Using real-time polymerase chain reaction analysis, we measured alterations in the relative gene expression of corticotropin-releasing factor in the paraventricular nucleus, pro-opiomelanocortin in the arcuate nucleus of the hypothalamus, glucocorticoid receptor in the hippocampus, and serotonin 5-HTR1A receptor in the hippocampus and amygdala. [Results]: Under baseline conditions, cannabidiol did not modify any element of the hypothalamus-pituitary-adrenal axis. In contrast, all doses induced alterations in 5-HTR1A in the amygdala and hippocampus. Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression. Also, restraint stress induced the opposite effects in 5-HTR1A gene expression in the hippocampus and amygdala, an effect not seen in mice treated with cannabidiol at low doses. [Conclusions]: Taken together, these data suggest the ability of cannabidiol to regulate acute stress hypothalamus-pituitary-adrenal axis activation might be explained, at least in part, by its action on 5-HTR1A receptors. |
| Databáze: | OpenAIRE |
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