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Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analg...

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Autores principales: Paul, Alok K., Gueven, Nuri, Dietis, Nikolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308092/
https://www.ncbi.nlm.nih.gov/pubmed/34299631
http://dx.doi.org/10.3390/molecules26144355
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author Paul, Alok K.
Gueven, Nuri
Dietis, Nikolas
author_facet Paul, Alok K.
Gueven, Nuri
Dietis, Nikolas
author_sort Paul, Alok K.
collection PubMed
description Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.
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spelling pubmed-83080922021-07-25 Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats Paul, Alok K. Gueven, Nuri Dietis, Nikolas Molecules Article Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance. MDPI 2021-07-19 /pmc/articles/PMC8308092/ /pubmed/34299631 http://dx.doi.org/10.3390/molecules26144355 Text en © 2021 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
Paul, Alok K.
Gueven, Nuri
Dietis, Nikolas
Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title_full Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title_fullStr Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title_full_unstemmed Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title_short Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats
title_sort profiling the effects of repetitive morphine administration on motor behavior in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308092/
https://www.ncbi.nlm.nih.gov/pubmed/34299631
http://dx.doi.org/10.3390/molecules26144355
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