Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.

<h4>Background</h4>ɣ-aminobutyric acid (GABA) facilitator valproic acid may be able to curb memory disruption induced by morphine exposure.<h4>Objective</h4>The effects of the GABA facilitator valproic acid on the behavioral tolerance induced by morphine were investigated. Th...

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Autores principales: Ghazaleh Ghamkharinejad, Seyed Hossein Marashi, Forough Foolad, Mohammad Javan, Yaghoub Fathollahi
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:d90c90d9e2334264a967ac705ea83b852021-12-02T20:14:45ZUnconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.1932-620310.1371/journal.pone.0253902https://doaj.org/article/d90c90d9e2334264a967ac705ea83b852021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253902https://doaj.org/toc/1932-6203<h4>Background</h4>ɣ-aminobutyric acid (GABA) facilitator valproic acid may be able to curb memory disruption induced by morphine exposure.<h4>Objective</h4>The effects of the GABA facilitator valproic acid on the behavioral tolerance induced by morphine were investigated. Then hippocampal-dependent tasks named spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Finally, the changes in the expression of hippocampal GABA-A receptors underlying morphine tolerance were also examined.<h4>Methods</h4>Rats were treated with daily morphine injections, with or without distinct contextual pairing. To examine the effect of valproic acid on morphine tolerance expression, valproic acid was pretreated an hour before morphine. Spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Afterwards the changes in the expression of hippocampal GABAα receptors using the quantitative real-time PCR and western blot techniques to detect GABArα subunits mRNAs and protein level were studied.<h4>Results</h4>Our results showed that both learned and non-associative morphine tolerance influence short-term memory and the subjacent expression of GABArα mRNAs and protein level. Despite its attenuating effects on the development and expression of both learned and non-associative morphine tolerance, only associative morphine tolerance-induced memory dysfunction was ameliorated by valproic acid pretreatment. We also found that the expression of GABArα1, α2, α5 subunits mRNAs and GABAα protein level were affected heavier in associative morphine tolerant rats.<h4>Conclusion</h4>Our data supports the hypothesis that unconditioned and learned morphine tolerance influences short-term memory and the expression of GABArα 1, α2, α5 mRNAs and GABArα protein level differently, and adds to our understanding of the behavioral and molecular aspects of the learned tolerance to morphine effects.Ghazaleh GhamkharinejadSeyed Hossein MarashiForough FooladMohammad JavanYaghoub FathollahiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0253902 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ghazaleh Ghamkharinejad
Seyed Hossein Marashi
Forough Foolad
Mohammad Javan
Yaghoub Fathollahi
Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
description <h4>Background</h4>ɣ-aminobutyric acid (GABA) facilitator valproic acid may be able to curb memory disruption induced by morphine exposure.<h4>Objective</h4>The effects of the GABA facilitator valproic acid on the behavioral tolerance induced by morphine were investigated. Then hippocampal-dependent tasks named spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Finally, the changes in the expression of hippocampal GABA-A receptors underlying morphine tolerance were also examined.<h4>Methods</h4>Rats were treated with daily morphine injections, with or without distinct contextual pairing. To examine the effect of valproic acid on morphine tolerance expression, valproic acid was pretreated an hour before morphine. Spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Afterwards the changes in the expression of hippocampal GABAα receptors using the quantitative real-time PCR and western blot techniques to detect GABArα subunits mRNAs and protein level were studied.<h4>Results</h4>Our results showed that both learned and non-associative morphine tolerance influence short-term memory and the subjacent expression of GABArα mRNAs and protein level. Despite its attenuating effects on the development and expression of both learned and non-associative morphine tolerance, only associative morphine tolerance-induced memory dysfunction was ameliorated by valproic acid pretreatment. We also found that the expression of GABArα1, α2, α5 subunits mRNAs and GABAα protein level were affected heavier in associative morphine tolerant rats.<h4>Conclusion</h4>Our data supports the hypothesis that unconditioned and learned morphine tolerance influences short-term memory and the expression of GABArα 1, α2, α5 mRNAs and GABArα protein level differently, and adds to our understanding of the behavioral and molecular aspects of the learned tolerance to morphine effects.
format article
author Ghazaleh Ghamkharinejad
Seyed Hossein Marashi
Forough Foolad
Mohammad Javan
Yaghoub Fathollahi
author_facet Ghazaleh Ghamkharinejad
Seyed Hossein Marashi
Forough Foolad
Mohammad Javan
Yaghoub Fathollahi
author_sort Ghazaleh Ghamkharinejad
title Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
title_short Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
title_full Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
title_fullStr Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
title_full_unstemmed Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits.
title_sort unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of gaba-a receptor alpha subunits.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/d90c90d9e2334264a967ac705ea83b85
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