Sex-dependent effects of in utero cannabinoid exposure on cortical function
- Aix-Marseille University, INSERM, INMED, France
- University Roma Tre, Italy
- INSERM-Indiana University, United States
Abstract
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.
Data availability
The processed data for the qPCR, behavior and electrophysiological data generated during the course of our study have been provided as Source Data.
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Author details
Funding
Institut National de la Santé et de la Recherche Médicale
- Michela Serviado
Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Milene Borsoi
Agence Nationale de la Recherche (Cannado)
- Anissa Bara
- Anne-Laure Pelissier-Alicot
- Olivier J Manzoni
Fondation pour la Recherche Médicale (Equipe FRM 2015)
- Anissa Bara
- Milene Borsoi
- Olivier J Manzoni
National Institutes of Health (5R01DA043982-02)
- Ken Mackie
- Olivier J Manzoni
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were treated in compliance with the European Communities Council Directive (86/609/EEC) and the United States National Institutes of Health Guide for the care and use of laboratory animals.
Copyright
© 2018, Bara et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sex-dependent effects of in utero cannabinoid exposure on cortical function
eLife 7:e36234.
https://doi.org/10.7554/eLife.36234
