Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus

Marieka V. DeVuono; Mina G. Nashed; Mohammed H. Sarikahya; Andrea Kocsis; Kendrick Lee; Sebastian R. Vanin; Roger Hudson; Eryn P. Lonnee; Walter J. Rushlow; Daniel B. Hardy; Steven R. Laviolette

Neurobiology of Disease (Sep 2024)

Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus

Marieka V. DeVuono,
Mina G. Nashed,
Mohammed H. Sarikahya,
Andrea Kocsis,
Kendrick Lee,
Sebastian R. Vanin,
Roger Hudson,
Eryn P. Lonnee,
Walter J. Rushlow,
Daniel B. Hardy,
Steven R. Laviolette

Affiliations

Marieka V. DeVuono: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada; Corresponding author at: 468 Medical Science Building, Dept. of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, Canada.
Mina G. Nashed: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada
Mohammed H. Sarikahya: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada
Andrea Kocsis: Dept of Physiology & Pharmacology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Obstetrics & Gynecology, University of Western Ontario, London, ON N6A 3K7, Canada
Kendrick Lee: Dept of Physiology & Pharmacology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Obstetrics & Gynecology, University of Western Ontario, London, ON N6A 3K7, Canada
Sebastian R. Vanin: Dept of Physiology & Pharmacology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Obstetrics & Gynecology, University of Western Ontario, London, ON N6A 3K7, Canada
Roger Hudson: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada
Eryn P. Lonnee: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada
Walter J. Rushlow: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Psychiatry, University of Western Ontario, London, ON N6A 3K7, Canada
Daniel B. Hardy: Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Physiology & Pharmacology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Obstetrics & Gynecology, University of Western Ontario, London, ON N6A 3K7, Canada; Division of Maternal, Fetal and Newborn Health, Children's Health Research Institute (CHRI), Lawson Health Research Institute, St. Joseph's Health Care, London, ON N6C 2R5, Canada
Steven R. Laviolette: Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada; Dept of Anatomy & Cell Biology, University of Western Ontario, London, ON N6A 3K7, Canada; Dept of Psychiatry, University of Western Ontario, London, ON N6A 3K7, Canada; Division of Maternal, Fetal and Newborn Health, Children's Health Research Institute (CHRI), Lawson Health Research Institute, St. Joseph's Health Care, London, ON N6C 2R5, Canada

Journal volume & issue: Vol. 199
p. 106588

Abstract

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Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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