Staff View: Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism

Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism

Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward syste...

Full description

Saved in:

Bibliographic Details
Main Authors:	Ismail, Nurul Iman, Ahmad, Nur Aimi Zawami, Mohd Yusof, Nurul Aiman, Talib, Ummi Nasrah, Norazit, Anwar, Kumar, Jaya, Mehat, Muhammad Zulfadli, Hassan, Zurina, Muller, Christian P., Muzaimi, Mustapha
Format:	Article
Published:	Frontiers Media 2021
Tags:	Add Tag No Tags, Be the first to tag this record!

id	oai:psasir.upm.edu.my:94208
record_format	eprints
spelling	oai:psasir.upm.edu.my:94208 http://psasir.upm.edu.my/id/eprint/94208/ Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism Ismail, Nurul Iman Ahmad, Nur Aimi Zawami Mohd Yusof, Nurul Aiman Talib, Ummi Nasrah Norazit, Anwar Kumar, Jaya Mehat, Muhammad Zulfadli Hassan, Zurina Muller, Christian P. Muzaimi, Mustapha Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward system. Its chronic administration is associated with cognitive impairments in animal studies. However, the underlying molecular mechanism for such a deficit remains elusive. In this study, the involvement of cannabinoid type-1 (CB1) receptors in cognitive deficits after chronic mitragynine exposures was investigated for 28 days (with incremental dose sensitization from 1 to 25 mg/kg) in adult male Swiss albino mice using the IntelliCage® system. Chronic high-dose mitragynine exposure (5–25 mg/kg, intraperitoneal [i.p.]), but not low-dose exposure (1–4 mg/kg, i.p.), induced hyperlocomotion, potentiated the preference for sucrose reward, increased resistance to punishment, and impaired place learning and its reversal. Comparable deficits were also observed after chronic treatments with Δ-9-tetrahydrocannabinol (THC, 2 mg/kg, i.p.) or morphine (5 mg/kg, subcutaneous). Mitragynine-, morphine-, and THC-induced learning and memory deficits were reversed by co-treatment with the CB1 receptor antagonist, NIDA-41020 (10 mg/kg, i.p.). A significant upregulation of CB1 receptor expression was found in the hippocampal CA1 region and ventral tegmental area after chronic high-dose mitragynine and morphine, whereas a downregulation was observed after chronic THC. In conclusion, the present study suggests a plausible role of the CB1 receptor in mediating the dose-dependent cognitive deficits after chronic high-dose mitragynine exposure. This also highlights the potential of CB1 receptor antagonism in ameliorating the cognitive deficits associated with long-term kratom/mitragynine consumption in humans. Frontiers Media 2021-09-16 Article PeerReviewed Ismail, Nurul Iman and Ahmad, Nur Aimi Zawami and Mohd Yusof, Nurul Aiman and Talib, Ummi Nasrah and Norazit, Anwar and Kumar, Jaya and Mehat, Muhammad Zulfadli and Hassan, Zurina and Muller, Christian P. and Muzaimi, Mustapha (2021) Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism. Frontiers in Pharmacology, 12. art. no. 708055. pp. 1-21. ISSN 1663-9812 https://www.frontiersin.org/articles/10.3389/fphar.2021.708055/full 10.3389/fphar.2021.708055
institution	UPM IR
collection	UPM IR
description	Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward system. Its chronic administration is associated with cognitive impairments in animal studies. However, the underlying molecular mechanism for such a deficit remains elusive. In this study, the involvement of cannabinoid type-1 (CB1) receptors in cognitive deficits after chronic mitragynine exposures was investigated for 28 days (with incremental dose sensitization from 1 to 25 mg/kg) in adult male Swiss albino mice using the IntelliCage® system. Chronic high-dose mitragynine exposure (5–25 mg/kg, intraperitoneal [i.p.]), but not low-dose exposure (1–4 mg/kg, i.p.), induced hyperlocomotion, potentiated the preference for sucrose reward, increased resistance to punishment, and impaired place learning and its reversal. Comparable deficits were also observed after chronic treatments with Δ-9-tetrahydrocannabinol (THC, 2 mg/kg, i.p.) or morphine (5 mg/kg, subcutaneous). Mitragynine-, morphine-, and THC-induced learning and memory deficits were reversed by co-treatment with the CB1 receptor antagonist, NIDA-41020 (10 mg/kg, i.p.). A significant upregulation of CB1 receptor expression was found in the hippocampal CA1 region and ventral tegmental area after chronic high-dose mitragynine and morphine, whereas a downregulation was observed after chronic THC. In conclusion, the present study suggests a plausible role of the CB1 receptor in mediating the dose-dependent cognitive deficits after chronic high-dose mitragynine exposure. This also highlights the potential of CB1 receptor antagonism in ameliorating the cognitive deficits associated with long-term kratom/mitragynine consumption in humans.
format	Article
author	Ismail, Nurul Iman Ahmad, Nur Aimi Zawami Mohd Yusof, Nurul Aiman Talib, Ummi Nasrah Norazit, Anwar Kumar, Jaya Mehat, Muhammad Zulfadli Hassan, Zurina Muller, Christian P. Muzaimi, Mustapha
spellingShingle	Ismail, Nurul Iman Ahmad, Nur Aimi Zawami Mohd Yusof, Nurul Aiman Talib, Ummi Nasrah Norazit, Anwar Kumar, Jaya Mehat, Muhammad Zulfadli Hassan, Zurina Muller, Christian P. Muzaimi, Mustapha Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
author_facet	Ismail, Nurul Iman Ahmad, Nur Aimi Zawami Mohd Yusof, Nurul Aiman Talib, Ummi Nasrah Norazit, Anwar Kumar, Jaya Mehat, Muhammad Zulfadli Hassan, Zurina Muller, Christian P. Muzaimi, Mustapha
author_sort	Ismail, Nurul Iman
title	Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
title_short	Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
title_full	Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
title_fullStr	Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
title_full_unstemmed	Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism
title_sort	mitragynine (kratom)-induced cognitive impairments in mice resemble δ9-thc and morphine effects: reversal by cannabinoid cb1 receptor antagonism
publisher	Frontiers Media
publishDate	2021
_version_	1782761309826187264
score	12.933938

Mitragynine (Kratom)-induced cognitive impairments in mice resemble Δ9-THC and morphine effects: reversal by cannabinoid CB1 receptor antagonism

Similar Items