The Effects of Peripubertal THC Exposure in Neurodevelopmental
Rat Models of Psychopathology

J 2023

The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

DI BARTOLOMEO, Martina, Tibor ŠTARK, Serena DI MARTINO, Fabio Arturo IANNOTTI, Jana RUDÁ et. al.

Základní údaje

Originální název

The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

Název česky

Vliv peripublertální expoyice THC v neurovývojových potkaních modelech psychopatologie

Autoři

DI BARTOLOMEO, Martina (380 Itálie), Tibor ŠTARK (703 Slovensko, domácí), Serena DI MARTINO (380 Itálie), Fabio Arturo IANNOTTI (380 Itálie), Jana RUDÁ (203 Česká republika, garant, domácí), Giovanni Luca ROMANO (380 Itálie), Martin KUCHAR (203 Česká republika), Samuele LAUDANI (380 Itálie), Petr PALIVEC (203 Česká republika), Fabiana PISCITELLI (380 Itálie), Carsten T WOTJAK (276 Německo), Claudio BUCOLO (380 Itálie), Filippo DRAGO (380 Itálie), Vincenzo DI MARZO (380 Itálie), Claudio D'ADDARIO (380 Itálie) a Vincenzo MICALE (380 Itálie)

Vydání

International Journal of Molecular Sciences, Basel, MDPI, 2023, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600 v roce 2022

Kód RIV

RIV/00216224:14110/23:00130855

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/ijms24043907

UT WoS

000939912200001

Klíčová slova anglicky

tetra(9)-tetrahydrocannabinol; methylazoxymethanol acetate; dopamine; D2/D3 receptors; psychopathology

Štítky

14110516, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 2. 2024 14:35, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

MUNI/A/1342/2022, interní kód MU

Název: Preklinický a klinický výzkum v oblasti farmakokinetiky, neuropsychofarmakologie a personalizované farmakoterapie v onkologii

Investor: Masarykova univerzita, Preklinický a klinický výzkum v oblasti farmakokinetiky, neuropsychofarmakologie a personalizované farmakoterapie v onkologii

3SGA5789, interní kód MU

Název: PRECIPITATION OF SCHIZOPHRENIA-LIKE PHENOTYPE BY PRENATAL INFLUENCES: ASSESSING THE ROLE OF THE ENDOCANNABINOID SYSTEM (Akronym: ncRNAPain)

Investor: Jihomoravský kraj, PRECIPITATION OF SCHIZOPHRENIA-LIKE PHENOTYPE BY PRENATAL INFLUENCES: ASSESSING THE ROLE OF THE ENDOCANNABINOID SYSTEM, Granty pro zahraniční vědce

Citovat

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 a Vincenzo MICALE. The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology. International Journal of Molecular Sciences. Basel: MDPI, 2023, roč. 24, č. 4, s. 1-15. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms24043907.

@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 a Vincenzo MICALE. The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2023, roč.~24, č.~4, s.~1-15. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms24043907.

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