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.

Basic information

Original name

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

Name in Czech

Vliv peripublertální expoyice THC v neurovývojových potkaních modelech psychopatologie

Authors

DI BARTOLOMEO, Martina (380 Italy), Tibor ŠTARK (703 Slovakia, belonging to the institution), Serena DI MARTINO (380 Italy), Fabio Arturo IANNOTTI (380 Italy), Jana RUDÁ (203 Czech Republic, guarantor, belonging to the institution), Giovanni Luca ROMANO (380 Italy), Martin KUCHAR (203 Czech Republic), Samuele LAUDANI (380 Italy), Petr PALIVEC (203 Czech Republic), Fabiana PISCITELLI (380 Italy), Carsten T WOTJAK (276 Germany), Claudio BUCOLO (380 Italy), Filippo DRAGO (380 Italy), Vincenzo DI MARZO (380 Italy), Claudio D'ADDARIO (380 Italy) and Vincenzo MICALE (380 Italy)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600 in 2022

RIV identification code

RIV/00216224:14110/23:00130855

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000939912200001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1342/2022, interní kód MU

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

Investor: Masaryk University, Preclinical and clinical research in pharmacokinetics, neuropsychopharmacology and personalized pharmacotherapy in oncology

3SGA5789, interní kód MU

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

Investor: South-Moravian Region, Incoming grants

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 and Vincenzo MICALE. The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology. 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.

@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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