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

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 incomple...

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Bibliographic Details
Published in:	eLife Vol. 7
Main Authors:	Bara, Anissa, Manduca, Antonia, Bernabeu, Axel, Borsoi, Milene, Serviado, Michela, Lassalle, Olivier, Murphy, Michelle, Wager-Miller, Jim, Mackie, Ken, Pelissier-Alicot, Anne-Laure, Trezza, Viviana, Manzoni, Olivier J
Format:	Journal Article
Language:	English
Published:	England eLife Sciences Publications Ltd 11-09-2018 eLife Sciences Publication eLife Sciences Publications, Ltd
Subjects:	Addictive behaviors Allosteric properties Allosteric Regulation - drug effects Anandamide Animal cognition Animals Anxiety Anxiety - pathology Arachidonic Acids - metabolism Behavior Behavior, Animal Behavioral plasticity Brain Cannabinoids Cannabinoids - pharmacology Cannabis Emotional behavior Endocannabinoids - metabolism Excitability Female Fetuses Gender differences Gene expression Gene Expression Regulation, Developmental - drug effects Genetic crosses Gestation Glutamic acid receptors (metabotropic) in-utero Intrauterine exposure Life Sciences Long-term depression Long-Term Potentiation - drug effects Male Marijuana Memory mRNA Neuronal Plasticity - drug effects Neurons and Cognition Neuroscience Nucleus Accumbens - drug effects Nucleus Accumbens - pathology Placenta Polyunsaturated Alkamides - metabolism Prefrontal cortex Prefrontal Cortex - drug effects Prefrontal Cortex - pathology Prefrontal Cortex - physiopathology Pregnancy Prenatal experience Prenatal Exposure Delayed Effects - pathology Prenatal Exposure Delayed Effects - physiopathology Pyramidal cells Pyramidal Cells - drug effects Pyramidal Cells - metabolism Rats, Wistar Receptor, Cannabinoid, CB1 - metabolism Receptor, Metabotropic Glutamate 5 - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Sex Characteristics sex difference Social Behavior Social interaction Social Isolation Software Substance abuse treatment Synaptic plasticity TRPV Cation Channels - metabolism Marseille France Indiana France United States > US cannabis in-utero rat sex difference neuroscience social behavior
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Summary:	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.
Bibliography:	These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/elife.36234