Prenatal and early postnatal cannabis exposure interactions with adolescent chronic stress on anxiety-like, depression-like, and risk-taking behaviour.

Abstract

RATIONALE: Low socioeconomic status people make up a majority of those who use cannabis during pregnancy. Both developmental cannabis exposure and developmental stress increase the risk of developing psychiatric disorders; however, the interaction of these factors has not been studied. OBJECTIVES: This study examined whether prenatal and early postnatal cannabis exposure (PPCE) impacted susceptibility to chronic adolescent stress in a dose- and environment-controlled animal model. METHODS: Mouse dams orally consumed 5 mg/kg THC in whole cannabis oil daily from GD1-PD10. Offspring were exposed to chronic mild unpredictable stress throughout adolescence (PD28-56). From PD58, mice were challenged with a battery of tests to measure anxiety-like (elevated plus maze, open field test), stress coping (forced swim test, tail suspension test), anhedonia-like (sucrose preference), risk-taking behaviour (wire beam bridge), and social motivation (3 chamber sociability and social novelty task). Brain slices were taken 90 min after forced swim test to analyze c-Fos expression. RESULTS: PPCE did not interact with chronic adolescent stress to impact anxiety-like, acute stress coping, or social motivation. However, co-exposed mice showed a significantly increased incidence of bridge crossing in the wire beam bridge task, whereas stress-only exposed animals did not. There were sex differences in c-FOS expression in the prefrontal cortex (PFC) in response to stress and PPCE. CONCLUSIONS: These data indicate that PPCE, when combined with adolescent stress, increases risk-taking behaviour.