Sex-dependent effects of in utero cannabinoid exposure on cortical function

eLife

Jim Wager-Miller¹  Antonia Manduca²  Anne-Laure Pelissier-Alicot²  Milene Borsoi²  Michelle Murphy²  Michela Serviado³  Olivier Lassalle⁴  Axel Bernabeu⁴  Ken Mackie⁴  Anissa Bara⁴  Olivier J Manzoni⁴  Viviana Trezza⁵ 

[1] APHM, CHU Conception, Service de Psychiatrie, Marseille, France;Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States;Section of Biomedical Sciences and Technologies, Department of Science, University Roma Tre, Rome, Italy;Aix Marseille University, INSERM, INMED, Marseille, France;Section of Biomedical Sciences and Technologies, Department of Science, University Roma Tre, Rome, Italy;

关键词: cannabis;    in-utero;    sex difference;    social behavior;   

DOI  :  10.7554/eLife.36234

来源: DOAJ

【 摘 要 】

Cannabinoids can cross the placenta, thus may interfere with fetal endocannabinoid signaling during neurodevelopment, causing long-lasting deficits. Despite increasing reports of cannabis consumption during pregnancy, the protracted consequences of prenatal cannabinoid exposure (PCE) remain incompletely understood. Here, we report sex-specific differences in behavioral and neuronal deficits in the adult progeny of rat dams exposed to low doses of cannabinoids during gestation. In males, PCE reduced social interaction, ablated endocannabinoid long-term depression (LTD) and heightened excitability of prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and endocannabinoid signaling regulate emotional behavior and synaptic plasticity. Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of anandamide levels restored LTD and social interaction in PCE adult males. Together, these results highlight marked sexual differences in the effects of PCE and introduce strategies for reversing detrimental effects of PCE.

【 授权许可】

Unknown