Affiliation:
1. Translational Psychiatry Laboratory, Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC) Criciúma Santa Catarina Brazil
2. Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School University of Texas Health Science Center at Houston (UTHealth) Houston Texas USA
3. Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School University of Texas Health Science Center at Houston (UTHealth) Houston Texas USA
4. Neuroscience Graduate Program University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston Texas USA
Abstract
AbstractThis study aimed to evaluate Haloperidol's (Hal) effects on the behavioral, neurotrophic factors, and epigenetic parameters in an animal model of schizophrenia (SCZ) induced by ketamine (Ket). Injections of Ket or saline were administered intraperitoneal (once a day) between the 1st and 14th days of the experiment. Water or Hal was administered via gavage between the 8th and 14th experimental days. Thirty minutes after the last injection, the animals were subjected to behavioral analysis. The activity of DNA methyltransferase (DNMT), histone deacetylase (HDAC), and histone acetyltransferase and levels of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin‐3 (NT‐3), and glial‐derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum. Ket increased the covered distance and time spent in the central area of the open field, and Hal did not reverse these behavioral alterations. Significant increases in the DNMT and HDAC activities were detected in the frontal cortex and striatum from rats that received Ket, Hal, or a combination thereof. Besides, Hal per se increased the activity of DNMT and HDAC in the hippocampus of rats. Hal per se or the association of Ket plus Hal decreased BDNF, NGF, NT‐3, and GDNF, depending on the brain region and treatment regimen. The administration of Hal can alter the levels of neurotrophic factors and the activity of epigenetic enzymes, which can be a factor in the development of effect collateral in SCZ patients. However, the precise mechanisms involved in these alterations are still unclear.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
Instituto Mente e Cérebro - Neurociência
Universidade do Extremo Sul Catarinense
Subject
Developmental Biology,Developmental Neuroscience
Cited by
1 articles.
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