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.
|Number of pages||18|
|State||Published - 10 Feb 2021|
Bibliographical noteFunding Information:
Funding for this study was provided by The Binational Science Foundation (BSF) Grant no. 2015/084 to I.A. and C.J.H. (URL: www.bsf.org.il ). The BSF had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
© 2020 IBRO
- fatty acid amide hydrolase (FAAH) CB1 receptor
- glucocorticoid receptors
ASJC Scopus subject areas
- Neuroscience (all)