Mitragynine (Kratom)—Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism
Yunusa S, Müller CP, Hassan Z (2024)
Publication Type: Journal article
Publication year: 2024
Journal
DOI: 10.1111/bph.16352
Abstract
Background and Purpose: Kratom is a preparation from Mitragyna speciosa, which is used as a natural drug preparation for many purposes around the world. However, an overdose of Kratom may cause addiction-like problems including aversive withdrawal states resulting in cognitive impairments via unknown mechanisms. Its main psychoactive alkaloid is mitragynine, showing opioid-like properties. Experimental Approach: Here, we analysed the neuropharmacological effects of mitragynine compared with morphine withdrawal in rats and searched for a pharmacological treatment option that may reverse the occurring cognitive deficits that usually aggravate withdrawal. Key Results: We found that withdrawal from 14-day mitragynine (1–10 mg·kg−1·day−1) treatment caused dose-dependent behavioural withdrawal signs resembling those of morphine (5 mg·kg−1·day−1) withdrawal. However, mitragynine (5 and 10 mg·kg−1·day−1) withdrawal also induced impairments in a passive avoidance task. Mitragynine withdrawal not only reduced hippocampal field excitatory postsynaptic potential (fEPSP) amplitudes in basal synaptic transmission and long-term potentiation (LTP) but also reduced epigenetic markers, such as histone H3K9 and H4K12 expression. At the same time, it up-regulates HDAC2 expression. Targeting the epigenetic adaptations with the HDAC inhibitor, SAHA, reversed the effects of mitragynine withdrawal on epigenetic dysregulation, hippocampal input/output curves, paired-pulse facilitation, LTP and attenuated the cognitive deficit. However, SAHA amplified the effects of morphine withdrawal. Conclusion and Implications: The data from this work show that changes in histone expression and downstream hippocampal plasticity may explain mitragynine, but not morphine, withdrawal behaviours and cognitive impairments. Thus, it may provide a new treatment approach for aversive Kratom/mitragynine withdrawal and addiction.
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APA:
Yunusa, S., Müller, C.P., & Hassan, Z. (2024). Mitragynine (Kratom)—Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism. British Journal of Pharmacology. https://dx.doi.org/10.1111/bph.16352
MLA:
Yunusa, Suleiman, Christian P. Müller, and Zurina Hassan. "Mitragynine (Kratom)—Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism." British Journal of Pharmacology (2024).
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