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Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations...

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Autores principales: Uehara, Takashi, Kurachi, Masayoshi, Kondo, Takashi, Abe, Hitoshi, Itoh, Hiroko, Sumiyoshi, Tomiki, Suzuki, Michio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951253/
https://www.ncbi.nlm.nih.gov/pubmed/35330366
http://dx.doi.org/10.3390/jpm12030366
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author Uehara, Takashi
Kurachi, Masayoshi
Kondo, Takashi
Abe, Hitoshi
Itoh, Hiroko
Sumiyoshi, Tomiki
Suzuki, Michio
author_facet Uehara, Takashi
Kurachi, Masayoshi
Kondo, Takashi
Abe, Hitoshi
Itoh, Hiroko
Sumiyoshi, Tomiki
Suzuki, Michio
author_sort Uehara, Takashi
collection PubMed
description Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.
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spelling pubmed-89512532022-03-26 Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine Uehara, Takashi Kurachi, Masayoshi Kondo, Takashi Abe, Hitoshi Itoh, Hiroko Sumiyoshi, Tomiki Suzuki, Michio J Pers Med Article Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia. MDPI 2022-02-27 /pmc/articles/PMC8951253/ /pubmed/35330366 http://dx.doi.org/10.3390/jpm12030366 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Uehara, Takashi
Kurachi, Masayoshi
Kondo, Takashi
Abe, Hitoshi
Itoh, Hiroko
Sumiyoshi, Tomiki
Suzuki, Michio
Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title_full Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title_fullStr Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title_full_unstemmed Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title_short Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine
title_sort apocynin-tandospirone derivatives suppress methamphetamine-induced hyperlocomotion in rats with neonatal exposure to dizocilpine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951253/
https://www.ncbi.nlm.nih.gov/pubmed/35330366
http://dx.doi.org/10.3390/jpm12030366
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