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Elife. 2018 Sep 11;7. pii: e36234. doi: 10.7554/eLife.36234.

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

Author information

1
Aix Marseille University, INSERM, INMED, Marseille, France.
2
Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States.
3
Section of Biomedical Sciences and Technologies, Department of Science, University Roma Tre, Rome, Italy.
4
APHM, CHU Conception, Service de Psychiatrie, Marseille, France.
5
Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States.
6
Gill Centre, Indiana University, Bloomington, United States.
7
APHM, CHU Timone Adultes, Service de Médecine Légale, Marseille, France.
#
Contributed equally

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.

KEYWORDS:

cannabis; in-utero; neuroscience; rat; sex difference; social behavior

PMID:
30201092
PMCID:
PMC6162091
DOI:
10.7554/eLife.36234
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

AB, AM, AB, MB, MS, OL, MM, JW, KM, AP, VT No competing interests declared, OM Reviewing editor, eLife

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