Staff View: Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats

Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats

Rationale Kratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine...

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Main Authors:	Johari, Illa S., Harun, Norsyifa, Sofian, Zarif M., Shoaib, Mohammed
Format:	Article
Published:	Springer 2021
Subjects:	R Medicine (General) RM Therapeutics. Pharmacology
Online Access:	http://eprints.um.edu.my/26571/
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spelling	my.um.eprints.265712022-03-21T02:18:32Z http://eprints.um.edu.my/26571/ Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats Johari, Illa S. Harun, Norsyifa Sofian, Zarif M. Shoaib, Mohammed R Medicine (General) RM Therapeutics. Pharmacology Rationale Kratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine (MG), are limited. Objectives Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus. Methods Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration. Results Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points. Conclusion These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder. Springer 2021-11 Article PeerReviewed Johari, Illa S. and Harun, Norsyifa and Sofian, Zarif M. and Shoaib, Mohammed (2021) Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats. Psychopharmacology, 238 (11). pp. 3183-3191. ISSN 0033-3158, DOI https://doi.org/10.1007/s00213-021-05934-4 <https://doi.org/10.1007/s00213-021-05934-4>. 10.1007/s00213-021-05934-4
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine (General) RM Therapeutics. Pharmacology
spellingShingle	R Medicine (General) RM Therapeutics. Pharmacology Johari, Illa S. Harun, Norsyifa Sofian, Zarif M. Shoaib, Mohammed Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
description	Rationale Kratom (Mitragyna speciosa Korth), a native medicinal plant of Southeast Asia, is proposed to exhibit potential therapeutic value as an opioid substitute. However, studies of its negative emotional states resulting from withdrawal particularly of its main psychoactive compound, mitragynine (MG), are limited. Objectives Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus. Methods Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration. Results Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points. Conclusion These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.
format	Article
author	Johari, Illa S. Harun, Norsyifa Sofian, Zarif M. Shoaib, Mohammed
author_facet	Johari, Illa S. Harun, Norsyifa Sofian, Zarif M. Shoaib, Mohammed
author_sort	Johari, Illa S.
title	Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
title_short	Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
title_full	Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
title_fullStr	Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
title_full_unstemmed	Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
title_sort	pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats
publisher	Springer
publishDate	2021
url	http://eprints.um.edu.my/26571/
_version_	1735409429749170176
score	13.211869

Pentylenetetrazol-like stimulus is not produced following naloxone-precipitated mitragynine withdrawal in rats

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