Metabolic profile of methylazoxymethanol model of schizophrenia
in rats and effects of three antipsychotics in long-acting
formulation

J 2020

Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation

HORSKÁ, Kateřina, Hana KOTOLOVÁ, Michal KARPÍŠEK, Zuzana BABINSKÁ, Tomáš HAMMER et. al.

Basic information

Original name

Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation

Name in Czech

Metabolický profil tří antipsychotik v depotních formulacích u potkanů v methylazoxymethanolovém modelu schizofrenie

Authors

HORSKÁ, Kateřina (203 Czech Republic, belonging to the institution), Hana KOTOLOVÁ (203 Czech Republic, belonging to the institution), Michal KARPÍŠEK (203 Czech Republic, belonging to the institution), Zuzana BABINSKÁ (703 Slovakia, belonging to the institution), Tomáš HAMMER (203 Czech Republic, belonging to the institution), Jiří PROCHÁZKA (203 Czech Republic, belonging to the institution), Tibor ŠTARK (703 Slovakia, belonging to the institution), Vincenzo MICALE (380 Italy) and Jana RUDÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Toxicology and applied pharmacology, San Diego, Elsevier, 2020, 0041-008X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.219

RIV identification code

RIV/00216224:14110/20:00116401

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.taap.2020.115214

UT WoS

000580522200009

Keywords in English

Adipokine; Antipsychotic; Lipid Profile; Methylazoxymethanol; Rats

Abstract

V originále

Mortality in psychiatric patients with severe mental illnesses reaches a 2-3 times higher mortality rate compared to the general population, primarily due to somatic comorbidities. A high prevalence of cardiovascular morbidity can be attributed to the adverse metabolic effects of atypical antipsychotics (atypical APs), but also to metabolic dysregulation present in drug-naive patients. The metabolic aspects of neurodevelopmental schizophrenia-like models are understudied. This study evaluated the metabolic phenotype of a methylazoxymethanol (MAM) schizophrenia-like model together with the metabolic effects of three APs [olanzapine (OLA), risperidone (RIS) and haloperidol (HAL)] administered via long-acting formulations for 8 weeks in female rats. Body weight, feed efficiency, serum lipid profile, gastrointestinal and adipose tissue-derived hormones (leptin, ghrelin, glucagon and glucagon-like peptide 1) were determined. The lipid profile was assessed in APs-naive MAM and control cohorts of both sexes. Body weight was not altered by the MAM model, though cumulative food intake and feed efficiency was lowered in the MAM compared to CTR animals. The effect of the APs was also present; body weight gain was increased by OLA and RIS, while OLA induced lower weight gain in the MAM rats. Further, the MAM model showed lower abdominal adiposity, while OLA increased it. Serum lipid profile revealed MAM model-induced alterations in both sexes; total, HDL and LDL cholesterol levels were increased. The MAM model did not exert significant alterations in hormonal parameters except for elevation in leptin level. The results support intrinsic metabolic dysregulation in the MAM model in both sexes, but the MAM model did not manifest higher sensitivity to metabolic effects induced by antipsychotic treatment.

Links

MUNI/A/1292/2019, interní kód MU

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

Investor: Masaryk University, Category A

ROZV/28/LF19/2020, interní kód MU

Name: Regulace morfogeneze epitelu mléčné žlázy pomocí mechanických sil a dynamiky signalizace

Investor: Ministry of Education, Youth and Sports of the CR, Internal development projects

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

HORSKÁ, Kateřina, Hana KOTOLOVÁ, Michal KARPÍŠEK, Zuzana BABINSKÁ, Tomáš HAMMER, Jiří PROCHÁZKA, Tibor ŠTARK, Vincenzo MICALE and Jana RUDÁ. Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation. Toxicology and applied pharmacology. San Diego: Elsevier, 2020, vol. 406, November 2020, p. 1-14. ISSN 0041-008X. Available from: https://dx.doi.org/10.1016/j.taap.2020.115214.

@article{1678277,
   author = {Horská, Kateřina and Kotolová, Hana and Karpíšek, Michal and Babinská, Zuzana and Hammer, Tomáš and Procházka, Jiří and Štark, Tibor and Micale, Vincenzo and Rudá, Jana},
   article_location = {San Diego},
   article_number = {November 2020},
   doi = {http://dx.doi.org/10.1016/j.taap.2020.115214},
   keywords = {Adipokine; Antipsychotic; Lipid Profile; Methylazoxymethanol; Rats},
   language = {eng},
   issn = {0041-008X},
   journal = {Toxicology and applied pharmacology},
   title = {Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation},
   url = {https://www.sciencedirect.com/science/article/pii/S0041008X20303409?via%3Dihub},
   volume = {406},
   year = {2020}
}

TY  - JOUR
ID  - 1678277
AU  - Horská, Kateřina - Kotolová, Hana - Karpíšek, Michal - Babinská, Zuzana - Hammer, Tomáš - Procházka, Jiří - Štark, Tibor - Micale, Vincenzo - Rudá, Jana
PY  - 2020
TI  - Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation
JF  - Toxicology and applied pharmacology
VL  - 406
IS  - November 2020
SP  - 1-14
EP  - 1-14
PB  - Elsevier
SN  - 0041008X
KW  - Adipokine
KW  - Antipsychotic
KW  - Lipid Profile
KW  - Methylazoxymethanol
KW  - Rats
UR  - https://www.sciencedirect.com/science/article/pii/S0041008X20303409?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0041008X20303409?via%3Dihub
N2  - Mortality in psychiatric patients with severe mental illnesses reaches a 2-3 times higher mortality rate compared to the general population, primarily due to somatic comorbidities. A high prevalence of cardiovascular morbidity can be attributed to the adverse metabolic effects of atypical antipsychotics (atypical APs), but also to metabolic dysregulation present in drug-naive patients. The metabolic aspects of neurodevelopmental schizophrenia-like models are understudied. This study evaluated the metabolic phenotype of a methylazoxymethanol (MAM) schizophrenia-like model together with the metabolic effects of three APs [olanzapine (OLA), risperidone (RIS) and haloperidol (HAL)] administered via long-acting formulations for 8 weeks in female rats. Body weight, feed efficiency, serum lipid profile, gastrointestinal and adipose tissue-derived hormones (leptin, ghrelin, glucagon and glucagon-like peptide 1) were determined. The lipid profile was assessed in APs-naive MAM and control cohorts of both sexes. Body weight was not altered by the MAM model, though cumulative food intake and feed efficiency was lowered in the MAM compared to CTR animals. The effect of the APs was also present; body weight gain was increased by OLA and RIS, while OLA induced lower weight gain in the MAM rats. Further, the MAM model showed lower abdominal adiposity, while OLA increased it. Serum lipid profile revealed MAM model-induced alterations in both sexes; total, HDL and LDL cholesterol levels were increased. The MAM model did not exert significant alterations in hormonal parameters except for elevation in leptin level. The results support intrinsic metabolic dysregulation in the MAM model in both sexes, but the MAM model did not manifest higher sensitivity to metabolic effects induced by antipsychotic treatment.
ER  -

HORSKÁ, Kateřina, Hana KOTOLOVÁ, Michal KARPÍŠEK, Zuzana BABINSKÁ, Tomáš HAMMER, Jiří PROCHÁZKA, Tibor ŠTARK, Vincenzo MICALE and Jana RUDÁ. Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation. \textit{Toxicology and applied pharmacology}. San Diego: Elsevier, 2020, vol.~406, November 2020, p.~1-14. ISSN~0041-008X. Available from: https://dx.doi.org/10.1016/j.taap.2020.115214.

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