Sex-dependent effects of in utero cannabinoid exposure on cortical function
Anissa Bara,
Antonia Manduca,
Axel Bernabeu,
Milene Borsoi,
Michela Serviado,
Olivier Lassalle,
Michelle Murphy,
Jim Wager-Miller,
Ken Mackie,
Anne-Laure Pelissier-Alicot,
Viviana Trezza,
Olivier J Manzoni
Affiliations
Anissa Bara
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States
Antonia Manduca
Aix Marseille University, INSERM, INMED, 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
Axel Bernabeu
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States; APHM, CHU Conception, Service de Psychiatrie, Marseille, France
Milene Borsoi
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States
Michela Serviado
Section of Biomedical Sciences and Technologies, Department of Science, University Roma Tre, Rome, Italy
Olivier Lassalle
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States
Michelle Murphy
Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States; Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States; Gill Centre, Indiana University, Bloomington, United States
Jim Wager-Miller
Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States; Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States; Gill Centre, Indiana University, Bloomington, United States
Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States; Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States; Gill Centre, Indiana University, Bloomington, United States
Anne-Laure Pelissier-Alicot
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States; APHM, CHU Conception, Service de Psychiatrie, Marseille, France; APHM, CHU Timone Adultes, Service de Médecine Légale, Marseille, France
Viviana Trezza
Section of Biomedical Sciences and Technologies, Department of Science, University Roma Tre, Rome, Italy
Aix Marseille University, INSERM, INMED, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Indiana University, Indiana, United States
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.
