Estrogen recruits the endocannabinoid system to modulate emotionality

• Published in: Psychoneuroendocrinology Vol. 32; no. 4; pp. 350 - 357
• Main Authors: Hill, Matthew N, Karacabeyli, Eda S, Gorzalka, Boris B
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2007; Elsevier
• Subjects: Adult and adolescent clinical studies; Anandamide; Animals; Antidepressant; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Cannabinoid Receptor Modulators - physiology; Depression; Emotions - drug effects; Endocannabinoids; Endocrinology & Metabolism; Estrogens - pharmacology; Fatty acid amide hydrolase; Female; Fundamental and applied biological sciences. Psychology; Gender; Hormones and behavior; Maze Learning - drug effects; Medical sciences; Mood disorders; Neuropharmacology; Ovariectomy; Pharmacology. Drug treatments; Piperidines - pharmacology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Pyrazoles - pharmacology; Rats; Rats, Long-Evans; Swimming; Antidepressant; Fatty acid amide hydrolase; Depression; Gender; Anandamide; Mood disorder; Affect affectivity; Psychotropic; Arachidonic acid derivatives; Estrogen; Sex; Lipids; Emotion emotionality; Cannabinoid; Fatty acids; Ovarian hormone; Chemotherapy; Treatment; Endocannabinoid; Antidepressant agent; Sex steroid hormone
• DOI: 10.1016/j.psyneuen.2007.02.003
• ISSN: 0306-4530

Summary Estrogen administration elicits anxiolytic and antidepressant-like effects in female rats; however, the mechanism of this effect is unknown. Fatty acid amide hydrolase (FAAH), the enzyme which degrades the endocannabinoid anandamide, has been shown to be regulated by estrogen. Thus, we examined if the anxiolytic and antidepressant effects of estrogen implicated the endocannabinoid system. In the first experiment, ovariectomized female rats were administered a single injection of 17 β -estradiol (10 μg) or oil, and 48 h later were given an injection of the cannabinoid CB1 receptor antagonist AM251 (1 mg/kg) or vehicle. One hour after AM251 or vehicle administration, subjects were tested in either the open field test (OFT), elevated plus maze (EPM) or the forced swim test (FST). Estradiol treatment resulted in a significant increase in open arm entries in the EPM and time spent in the center quadrant of the OFT, which were reversed by co-treatment with AM251, suggesting that endocannabinoids are integral to the anxiolytic effects of estrogen. No significant effects of estradiol or AM251 were seen in the FST. In the second experiment, administration of the FAAH inhibitor URB597 (0.1 and 0.3 mg/kg) increased open arm entries in the EPM and time spent in the center quadrant in the OFT as well as significantly reduced immobility in the FST. Collectively, these data demonstrate that estrogen may elicit changes in emotional behavior through an endocannabinoid mechanism, and suggest that inhibition of FAAH represents a therapeutic target for anxiety and depression in women.