Iman, Ismail Nurul and Ahmad, Nur Aimi Zawami and Yusof, Nurul Aiman Mohd and Talib, Ummi Nasrah and Norazit, Anwar and Kumar, Jaya and Mehat, Muhammad Zulfadli and Hassan, Zurina and Mueller, Christian P. and Muzaimi, Mustapha (2021) Mitragynine (kratom)-induced cognitive impairments in mice resemble delta 9-THC and morphine effects: Reversal by cannabinoid CB1 receptor antagonism. Frontiers in Pharmacology, 12. ISSN 1663-9812, DOI https://doi.org/10.3389/fphar.2021.708055.
Full text not available from this repository.Abstract
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(R) 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 ?-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.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Sains Malaysia[304/PPSP/6315252], Universiti Sains Malaysia[1001/PPSP/8012300] |
| Uncontrolled Keywords: | Kratom;Mitragynine;Morphine;Delta 9-tetrahydrocannabinol (THC);Cannabinoid receptor 1 (CB1);Cognition |
| Subjects: | R Medicine R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 13 Sep 2022 01:14 |
| Last Modified: | 13 Sep 2022 01:14 |
| URI: | http://eprints.um.edu.my/id/eprint/34351 |
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