Format

Send to

Choose Destination
J Psychopharmacol. 2018 Dec;32(12):1379-1384. doi: 10.1177/0269881118805495. Epub 2018 Oct 16.

Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress.

Author information

1
1 Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
2
2 Red Temática de Investigación Cooperativa en Salud, Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain.

Abstract

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.

KEYWORDS:

Hypothalamus-pituitary-adrenal axis; acute restraint stress; cannabidiol; gene expression; real time polymerase chain reaction

PMID:
30324842
DOI:
10.1177/0269881118805495

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center