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

被引:0
|
作者
De Vuono, Marieka V. [1 ,2 ]
Nashed, Mina G. [1 ,2 ]
Sarikahya, Mohammed H. [1 ,2 ]
Kocsis, Andrea [3 ,4 ]
Lee, Kendrick [3 ,4 ]
Vanin, Sebastian R. [3 ,4 ]
Hudson, Roger [1 ,2 ]
Lonnee, Eryn P. [1 ,2 ]
Rushlow, Walter J. [1 ,2 ,5 ]
Hardy, Daniel B. [2 ,3 ,4 ,6 ]
Laviolette, Steven R. [1 ,2 ,5 ,6 ]
机构
[1] Univ Western Ontario, Schulich Sch Med & Dent, Addict Res Grp, London, ON N6A 5C1, Canada
[2] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 3K7, Canada
[3] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 3K7, Canada
[4] Univ Western Ontario, Dept Obstet & Gynecol, London, ON N6A 3K7, Canada
[5] Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada
[6] St Josephs Hlth Care, Childrens Hlth Res Inst CHRI, Lawson Hlth Res Inst, Div Maternal Fetal & Newborn Hlth, London, ON N6C 2R5, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Cannabis; Delta 9-tetrahydrocannabinol (THC); Cannabidiol (CBD); Pregnancy; Adolescence; Development; Prefrontal cortex; Ventral hippocampus; In vivo electrophysiology; RT-qPCR; INTRAUTERINE GROWTH RESTRICTION; ENDOCANNABINOID SYSTEM; VENTRAL HIPPOCAMPUS; 5-HT1A RECEPTOR; CANNABINOID AGONISTS; PREPULSE INHIBITION; MEMORY FORMATION; TEMPORAL-ORDER; MESSENGER-RNA; MARIJUANA USE;
D O I
10.1016/j.nbd.2024.106588
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (Delta 9-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 RTqPCR 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.
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页数:18
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