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@article{2286137,
author = {Di Bartolomeo, Martina and Štark, Tibor and Di Martino, Serena and Iannotti, Fabio Arturo and Rudá, Jana and Romano, Giovanni Luca and Kuchar, Martin and Laudani, Samuele and Palivec, Petr and Piscitelli, Fabiana and Wotjak, Carsten T and Bucolo, Claudio and Drago, Filippo and Di Marzo, Vincenzo and D'Addario, Claudio and Micale, Vincenzo},
article_location = {Basel},
article_number = {4},
doi = {http://dx.doi.org/10.3390/ijms24043907},
keywords = {tetra(9)-tetrahydrocannabinol; methylazoxymethanol acetate; dopamine; D2/D3 receptors; psychopathology},
language = {eng},
issn = {1422-0067},
journal = {International Journal of Molecular Sciences},
title = {The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology},
url = {https://www.mdpi.com/1422-0067/24/4/3907},
volume = {24},
year = {2023}
}
TY - JOUR
ID - 2286137
AU - Di Bartolomeo, Martina - Štark, Tibor - Di Martino, Serena - Iannotti, Fabio Arturo - Rudá, Jana - Romano, Giovanni Luca - Kuchar, Martin - Laudani, Samuele - Palivec, Petr - Piscitelli, Fabiana - Wotjak, Carsten T - Bucolo, Claudio - Drago, Filippo - Di Marzo, Vincenzo - D'Addario, Claudio - Micale, Vincenzo
PY - 2023
TI - The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
JF - International Journal of Molecular Sciences
VL - 24
IS - 4
SP - 1-15
EP - 1-15
PB - MDPI
SN - 14220067
KW - tetra(9)-tetrahydrocannabinol
KW - methylazoxymethanol acetate
KW - dopamine
KW - D2/D3 receptors
KW - psychopathology
UR - https://www.mdpi.com/1422-0067/24/4/3907
N2 - Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC) exposure in adult rats. We found that MAM and pTHC-exposed rats, when compared to the control group (CNT), were characterized by adult phenotype relevant to schizophrenia, including social withdrawal and cognitive impairment, as revealed by social interaction test and novel object recognition test, respectively. At the molecular level, we observed an increase in cannabinoid CB1 receptor (Cnr1) and/or dopamine D2/D3 receptor (Drd2, Drd3) gene expression in the prefrontal cortex of adult MAM or pTHC-exposed rats, which we attributed to changes in DNA methylation at key regulatory gene regions. Interestingly, aTHC treatment significantly impaired social behavior, but not cognitive performance in CNT groups. In pTHC rats, aTHC did not exacerbate the altered phenotype nor dopaminergic signaling, while it reversed cognitive deficit in MAM rats by modulating Drd2 and Drd3 gene expression. In conclusion, our results suggest that the effects of peripubertal THC exposure may depend on individual differences related to dopaminergic neurotransmission.
ER -
DI BARTOLOMEO, Martina, Tibor ŠTARK, Serena DI MARTINO, Fabio Arturo IANNOTTI, Jana RUDÁ, Giovanni Luca ROMANO, Martin KUCHAR, Samuele LAUDANI, Petr PALIVEC, Fabiana PISCITELLI, Carsten T WOTJAK, Claudio BUCOLO, Filippo DRAGO, Vincenzo DI MARZO, Claudio D'ADDARIO and Vincenzo MICALE. The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2023, vol.~24, No~4, p.~1-15. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms24043907.
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