TY - JOUR
T1 - Sex-dependent effects of in utero cannabinoid exposure on cortical function
AU - Bara, Anissa
AU - Manduca, Antonia
AU - Bernabeu, Axel
AU - Borsoi, Milene
AU - Serviado, Michela
AU - Lassalle, Olivier
AU - Murphy, Michelle
AU - Wager-Miller, Jim
AU - Mackie, Ken
AU - Pelissier-Alicot, Anne Laure
AU - Trezza, Viviana
AU - Manzoni, Olivier J.
N1 - Publisher Copyright:
© Bara et al.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054062112&partnerID=8YFLogxK
U2 - 10.7554/eLife.36234
DO - 10.7554/eLife.36234
M3 - Article
C2 - 30201092
AN - SCOPUS:85054062112
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e36234
ER -