Peripubertal cannabidiol treatment rescues behavioral and
neurochemical abnormalities in the MAM model of schizophrenia

J 2019

Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia

ŠTARK, Tibor, Jana RUDÁ, Fabio IANNOTI, Claudio D'ADDARIO, Roberta DI MARCO et. al.

Basic information

Original name

Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia

Authors

ŠTARK, Tibor (703 Slovakia, belonging to the institution), Jana RUDÁ (203 Czech Republic, guarantor, belonging to the institution), Fabio IANNOTI (380 Italy), Claudio D'ADDARIO (380 Italy), Roberta DI MARCO (380 Italy), Vladimír PEKAŘÍK (203 Czech Republic, belonging to the institution), Eva DRAŽANOVÁ (203 Czech Republic, belonging to the institution), Fabiana PISCITELLI (380 Italy), Monica BARI (380 Italy), Zuzana BABINSKÁ (703 Slovakia, belonging to the institution), Giovanni GIURDANELLA (380 Italy), Martina DI BARTOLOMEO (380 Italy), Salvatore SALOMONE (380 Italy), Alexandra ŠULCOVÁ (203 Czech Republic), Mauro MACCARRONE (380 Italy), Carsten WOTJAK (276 Germany), Zenon STARČUK (203 Czech Republic), Filippo DRAGO (380 Italy), Raphael MECHOULAM (376 Israel), Vincenzo DI MARZO (380 Italy) and Vincenzo MICALE (380 Italy, belonging to the institution)

Edition

Neuropharmacology, Oxford, Pergamon-Elsevier Science LTD, 2019, 0028-3908

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.431

RIV identification code

RIV/00216224:14110/19:00109798

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.neuropharm.2018.11.035

UT WoS

000457663900021

Keywords in English

Cannabidiol; Cannabinoid CB1 receptor; MAM model; Schizophrenia

Abstract

V originále

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the anti mitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1132/2017, interní kód MU

Name: Behaviorální psychofarmakologie a farmakokinetika v preklinickém výzkumu léčiv

Investor: Masaryk University, Category A

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

90062, large research infrastructures

Name: Czech-BioImaging

Citovat

ŠTARK, Tibor, Jana RUDÁ, Fabio IANNOTI, Claudio D'ADDARIO, Roberta DI MARCO, Vladimír PEKAŘÍK, Eva DRAŽANOVÁ, Fabiana PISCITELLI, Monica BARI, Zuzana BABINSKÁ, Giovanni GIURDANELLA, Martina DI BARTOLOMEO, Salvatore SALOMONE, Alexandra ŠULCOVÁ, Mauro MACCARRONE, Carsten WOTJAK, Zenon STARČUK, Filippo DRAGO, Raphael MECHOULAM, Vincenzo DI MARZO and Vincenzo MICALE. Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia. Neuropharmacology. Oxford: Pergamon-Elsevier Science LTD, 2019, vol. 146, No 1, p. 212-221. ISSN 0028-3908. Available from: https://dx.doi.org/10.1016/j.neuropharm.2018.11.035.

@article{1535717,
   author = {Štark, Tibor and Rudá, Jana and Iannoti, Fabio and D'Addario, Claudio and Di Marco, Roberta and Pekařík, Vladimír and Dražanová, Eva and Piscitelli, Fabiana and Bari, Monica and Babinská, Zuzana and Giurdanella, Giovanni and Di Bartolomeo, Martina and Salomone, Salvatore and Šulcová, Alexandra and Maccarrone, Mauro and Wotjak, Carsten and Starčuk, Zenon and Drago, Filippo and Mechoulam, Raphael and Di Marzo, Vincenzo and Micale, Vincenzo},
   article_location = {Oxford},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.neuropharm.2018.11.035},
   keywords = {Cannabidiol; Cannabinoid CB1 receptor; MAM model; Schizophrenia},
   language = {eng},
   issn = {0028-3908},
   journal = {Neuropharmacology},
   title = {Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia},
   url = {https://www.sciencedirect.com/science/article/pii/S0028390818308761},
   volume = {146},
   year = {2019}
}

TY  - JOUR
ID  - 1535717
AU  - Štark, Tibor - Rudá, Jana - Iannoti, Fabio - D'Addario, Claudio - Di Marco, Roberta - Pekařík, Vladimír - Dražanová, Eva - Piscitelli, Fabiana - Bari, Monica - Babinská, Zuzana - Giurdanella, Giovanni - Di Bartolomeo, Martina - Salomone, Salvatore - Šulcová, Alexandra - Maccarrone, Mauro - Wotjak, Carsten - Starčuk, Zenon - Drago, Filippo - Mechoulam, Raphael - Di Marzo, Vincenzo - Micale, Vincenzo
PY  - 2019
TI  - Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia
JF  - Neuropharmacology
VL  - 146
IS  - 1
SP  - 212-221
EP  - 212-221
PB  - Pergamon-Elsevier Science LTD
SN  - 00283908
KW  - Cannabidiol
KW  - Cannabinoid CB1 receptor
KW  - MAM model
KW  - Schizophrenia
UR  - https://www.sciencedirect.com/science/article/pii/S0028390818308761
L2  - https://www.sciencedirect.com/science/article/pii/S0028390818308761
N2  - In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the anti mitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At the molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression, which might be due to reduction in DNA methylation at the gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test and in the novel object recognition test in MAM rats. Both the schizophrenia-like phenotype and altered transcriptional regulation of CB1 receptors were reversed by peripubertal treatment (from PND 19 to PND 39) with the non-psychotropic phytocannabinoid cannabidiol (30 mg/kg/day), or, in part, by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day), but not with haloperidol (0.6 mg/kg/day). These results suggest that early treatment with cannabidiol may prevent both the appearance of schizophrenia-like deficits as well as CB1 alterations in the PFC at adulthood, supporting that peripubertal cannabidiol treatment might be protective against MAM insult.
ER  -

ŠTARK, Tibor, Jana RUDÁ, Fabio IANNOTI, Claudio D'ADDARIO, Roberta DI MARCO, Vladimír PEKAŘÍK, Eva DRAŽANOVÁ, Fabiana PISCITELLI, Monica BARI, Zuzana BABINSKÁ, Giovanni GIURDANELLA, Martina DI BARTOLOMEO, Salvatore SALOMONE, Alexandra ŠULCOVÁ, Mauro MACCARRONE, Carsten WOTJAK, Zenon STARČUK, Filippo DRAGO, Raphael MECHOULAM, Vincenzo DI MARZO and Vincenzo MICALE. Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia. \textit{Neuropharmacology}. Oxford: Pergamon-Elsevier Science LTD, 2019, vol.~146, No~1, p.~212-221. ISSN~0028-3908. Available from: https://dx.doi.org/10.1016/j.neuropharm.2018.11.035.

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