Sex-specific susceptibility to psychotic-like states provoked by prenatal THC exposure: Reversal by pregnenolone.
dopamine
introduction
neurosteroids
prenatal cannabis
schizophrenia
sensorimotor gating
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
23
01
2023
received:
01
08
2022
accepted:
02
02
2023
medline:
29
3
2023
pubmed:
23
2
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Sociocultural attitudes towards cannabis legalization contribute to the common misconception that it is a relatively safe drug and its use during pregnancy poses no risk to the fetus. However, longitudinal studies demonstrate that maternal cannabis exposure results in adverse outcomes in the offspring, with a heightened risk for developing psychopathology. One of the most reported psychiatric outcomes is the proneness to psychotic-like experiences during childhood. How exposure to cannabis during gestation increases psychosis susceptibility in children and adolescents remains elusive. Preclinical research has indicated that in utero exposure to the major psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), deranges brain developmental trajectories towards vulnerable psychotic-like endophenotypes later in life. Here, we present how prenatal THC exposure (PCE) deregulates mesolimbic dopamine development predisposing the offspring to schizophrenia-relevant phenotypes, exclusively when exposed to environmental challenges, such as stress or THC. Detrimental effects of PCE are sex-specific because female offspring do not display psychotic-like outcomes upon exposure to these challenges. Moreover, we present how pregnenolone, a neurosteroid that showed beneficial properties on the effects elicited by cannabis intoxication, normalizes mesolimbic dopamine function and rescues psychotic-like phenotypes. We, therefore, suggest this neurosteroid as a safe "disease-modifying" aid to prevent the onset of psychoses in vulnerable individuals. Our findings corroborate clinical evidence and highlight the relevance of early diagnostic screening and preventative strategies for young individuals at risk for mental diseases, such as male PCE offspring.
Substances chimiques
Pregnenolone
73R90F7MQ8
Dopamine
VTD58H1Z2X
Neurosteroids
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13240Informations de copyright
© 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.
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