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

Anissa Bara (1) , Antonia Manduca (1) , Axel Bernabeu (1) , Milene Borsoi (1) , Michela Serviado , Olivier Lassalle (1) , Michelle Murphy , Jim Wager-Miller , Ken Mackie , Anne-Laure Pélissier-Alicot (1, 2) , Viviana Trezza , Olivier Manzoni (1)

1 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
2 APHM - Assistance Publique - Hôpitaux de Marseille

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.

Domaines: Neurosciences [q-bio.NC]

Anissa Bara, Antonia Manduca, Axel Bernabeu, Milene Borsoi, Michela Serviado, et al.. Sex-dependent effects of in utero cannabinoid exposure on cortical function. eLife, 2018, 7, ⟨10.7554/eLife.36234⟩. ⟨hal-02079440⟩