Cannabinoid Exposure via Lactation in Rats Disrupts Perinatal Programming of the Gamma-Aminobutyric Acid Trajectory and Select Early-Life Behaviors.

Autor: Scheyer AF; Institut de neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U1249, Marseille, France; Aix-Marseille University, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University., Borsoi M; Institut de neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U1249, Marseille, France; Aix-Marseille University, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University., Wager-Miller J; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University; Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana., Pelissier-Alicot AL; Institut de neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U1249, Marseille, France; Aix-Marseille University, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University; Service de Psychiatrie, CHU Conception, Assistance Publique - Hôpitaux de Marseille, Marseille, France; Service de Médecine Légale, CHU Timone-Adultes, Assistance Publique - Hôpitaux de Marseille, Marseille, France., Murphy MN; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University; Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana., Mackie K; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University; Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana. Electronic address: kmackie@indiana.edu., Manzoni OJJ; Institut de neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U1249, Marseille, France; Aix-Marseille University, Marseille, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, Institut National de la Santé et de la Recherche Médicale-Aix-Marseille University/Indiana University. Electronic address: olivier.manzoni@inserm.fr.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2020 Apr 01; Vol. 87 (7), pp. 666-677. Date of Electronic Publication: 2019 Sep 05.
DOI: 10.1016/j.biopsych.2019.08.023
Abstrakt: Background: Cannabis usage is increasing with its widespread legalization. Cannabis use by mothers during lactation transfers active cannabinoids to the developing offspring during this critical period and alters postnatal neurodevelopment. A key neurodevelopmental landmark is the excitatory to inhibitory gamma-aminobutyric acid (GABA) switch caused by reciprocal changes in expression ratios of the K + /Cl - transporters potassium-chloride cotransporter 2 (KCC2) and sodium-potassium-chloride transporter (NKCC1).
Methods: Rat dams were treated with Δ 9 -tetrahydrocannabinol or a synthetic cannabinoid during the first 10 days of postnatal development, and experiments were then conducted in the offspring exposed to these drugs via lactation. The network influence of GABA transmission was analyzed using cell-attached recordings. KCC2 and NKCC1 levels were determined using Western blot and quantitative polymerase chain reaction analyses. Ultrasonic vocalization and homing behavioral experiments were carried out at relevant time points.
Results: Treating rat dams with cannabinoids during early lactation retards transcriptional upregulation and expression of KCC2, thereby delaying the GABA switch in pups of both sexes. This perturbed trajectory was corrected by the NKCC1 antagonist bumetanide and accompanied by alterations in ultrasonic vocalization without changes in homing behavior. Neurobehavioral deficits were prevented by CB 1 receptor antagonism during maternal exposure, showing that the CB 1 receptor underlies the cannabinoid-induced alterations.
Conclusions: These results reveal how perinatal cannabinoid exposure retards an early milestone of development, delaying the trajectory of GABA's polarity transition and altering early-life communication.
(Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: