Faculty Collaboration Database

Inhibition of Fatty Acid Amide Hydrolase (FAAH) During Adolescence and Exposure to Early Life Stress may Exacerbate Depression-like Behaviors in Male and Female Rats. Neuroscience 2021 Feb 10;455:89-106

Date

12/29/2020

Pubmed ID

33359656

DOI

10.1016/j.neuroscience.2020.12.022

Scopus ID

2-s2.0-85098975643 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

Early-life stress (ELS) is associated with later onset of depression. Early cannabis use may be a risk factor that interacts with environmental factors to increase the risk of psychopathologies. We aimed to examine the long-term effects of ELS on depression- and anxiety-like behavior, and examine whether chronic fatty acid amide hydrolase (FAAH) inhibition during mid-adolescence could ameliorate or exacerbate ELS effects on behavior. Male and female rats were exposed to ELS during post-natal days (P) 7-14, injected with the FAAH inhibitor URB597 (0.4 mg/kg, i.p.) or vehicle for 2 weeks during mid-adolescence (P30-45) or late-adolescence (P45-60). Rats were tested in adulthood for behavior and alterations in CB1 receptors (CB1r) and glucocorticoid receptors (GRs) in the brains' stress circuit. ELS produced decreased social preference, impaired social recognition, increased learned helplessness and anxiety-like behavior. Administering URB597 during mid-adolescence did not prevent the deleterious long-term effects of ELS on behavior in males and females. When URB597 was administered during late-adolescence, it ameliorated ELS-induced depression- and anxiety-like behavior. Moreover, in males, ELS and URB597 decreased CB1r levels in the prefrontal cortex (PFC) and CA1 and GRs in the PFC and basolateral amygdala (BLA). In females, ELS and URB decreased CB1r in the BLA and GRs in the CA1 and BLA. The findings suggest that mid-adolescence, as opposed to late-adolescence, may not be a potential developmental period for chronic treatment with FAAH inhibitors and that sex-dependent alterations in CB1r and GRs expression in the BLA-PFC-CA1 circuit may contribute to the depressive behavioral phenotype.

Author List

Alteba S, Portugalov A, Hillard CJ, Akirav I

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amidohydrolases
Animals
Depression
Endocannabinoids
Female
Male
Rats
Receptor, Cannabinoid, CB1
Stress, Psychological