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

Author

Michela Serviado, Olivier J. Manzoni, Michelle Murphy, Jim Wager-Miller, Viviana Trezza, Anissa Bara, Anne-Laure Pelissier-Alicot, Olivier Lassalle, Antonia Manduca, Milene Borsoi, Ken Mackie, Axel Bernabeu, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Molinari, Florence, Bara, A., Manduca, A., Bernabeu, A., Borsoi, M., Serviado, M., Lassalle, O., Murphy, M., Wager-Miller, J., Mackie, K., Pelissier-Alicot, A. -L., Trezza, V., and Manzoni, O. J.

Subjects
0301 basic medicine, Male, cannabis, Nucleus Accumben, medicine.medical_treatment, Long-Term Potentiation, Anxiety, neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Pregnancy, rat, Biology (General), Prefrontal cortex, Sex Characteristics, Arachidonic Acid, Neuronal Plasticity, Behavior, Animal, TRPV Cation Channel, General Neuroscience, Gene Expression Regulation, Developmental, General Medicine, Anandamide, Endocannabinoid system, 3. Good health, in-utero, Social Isolation, Metabotropic glutamate receptor 1, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, cannabi, QH301-705.5, Receptor, Metabotropic Glutamate 5, sex difference, Science, Prefrontal Cortex, Polyunsaturated Alkamide, General Biochemistry, Genetics and Molecular Biology, Prenatal Exposure Delayed Effect, social behavior, 03 medical and health sciences, Allosteric Regulation, Internal medicine, medicine, RNA, Messenger, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, Cannabinoid, Endocannabinoid, Fetus, General Immunology and Microbiology, business.industry, Animal, 030104 developmental biology, Endocrinology, chemistry, Metabotropic glutamate receptor, Synaptic plasticity, Pyramidal Cell, business, 030217 neurology & neurosurgery
Abstract

International audience; 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.

Published
2018

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

Author

Bara A, Manduca A, Bernabeu A, Borsoi M, Serviado M, Lassalle O, Murphy M, Wager-Miller J, Mackie K, Pelissier-Alicot AL, Trezza V, and Manzoni OJ

Subjects
Allosteric Regulation drug effects, Animals, Anxiety pathology, Arachidonic Acids metabolism, Behavior, Animal, Endocannabinoids metabolism, Female, Gene Expression Regulation, Developmental drug effects, Long-Term Potentiation drug effects, Male, Neuronal Plasticity drug effects, Nucleus Accumbens drug effects, Nucleus Accumbens pathology, Polyunsaturated Alkamides metabolism, Prefrontal Cortex drug effects, Prefrontal Cortex pathology, Pregnancy, Pyramidal Cells drug effects, Pyramidal Cells metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Wistar, Receptor, Cannabinoid, CB1 metabolism, Receptor, Metabotropic Glutamate 5 metabolism, Social Behavior, Social Isolation, TRPV Cation Channels metabolism, Cannabinoids pharmacology, Prefrontal Cortex physiopathology, Prenatal Exposure Delayed Effects pathology, Prenatal Exposure Delayed Effects physiopathology, Sex Characteristics
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., Competing Interests: AB, AM, AB, MB, MS, OL, MM, JW, KM, AP, VT No competing interests declared, OM Reviewing editor, eLife, (© 2018, Bara et al.)

Published
2018
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