Behavioural Effects And Brain Activity Of Mitragynine From Mitragyna Speciosa Korth (Kratom) On Learning And Memory Functions In Rat
Loading...
Date
2015-12
Authors
Suhaimi, Farah Wahida
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Mitragynine, the major alkaloid from Mitragyna speciosa Korth has been widely studied for its pharmacological effects. However, little is known about its effects on learning and memory functions. In present study, the acute effects of mitragynine on different stages of learning and memory processes were investigated. Pre-training, post-training and pre-test administration of mitragynine (1, 5 and 10 mg/kg) impaired the acquisition, memory consolidation and retrieval of the passive avoidance task, to a similar degree as morphine. The study further investigated if the effects of mitragynine are either task-dependent or common to other behavioural tasks. The results showed that mitragynine (5 and 10 mg/kg) caused spatial learning deficits and impaired reference memory in Morris water maze task. Then, chronic effects of mitragynine (28 days) on learning and memory functions were assessed. Results demonstrated that chronic mitragynine impaired memory retrieval of the passive avoidance task during early withdrawal and abstinence. Effects of mitragynine were further evaluated using novel object recognition task in the same treated-animals. The results indicated that animals were able to discriminate between the novel and familiar objects but the ability to remember the previously encountered object was attenuated in the animals treated with high dose of mitragynine (10 mg/kg). The results suggested that high dose of mitragynine is required to maintain the memory-impairing effects of mitragynine in a new learning task during abstinence. The effects of mitragynine on brain activity were further evaluated in chronically-treated animals for 28 days. Mitragynine caused dissociative patterns in EEG of both cortical tissues (frontal and neocortex) and hippocampus. Repeated exposure to equal dose of mitragynine at 10 mg/kg caused an increase in delta power and a decrease in alpha power in both frontal cortex and neocortex. On the contrary, repeated exposure to mitragynine regardless of the doses decreased the delta power but only mitragynine at 5 and 10 mg/kg decreased the alpha power in the hippocampus. These changes in EEG may suggest that mitragynine was able to challenge the local network stability. In addition, post-training administration of naloxone, an opioid antagonist (1.0 mg/kg) and bicuculline, GABAA antagonist (0.125 mg/kg) improved memory impairment induced by mitragynine, suggesting the participation of the opioidergic and GABAergic systems in modulating the effects of mitragynine in learning and memory functions. In Morris water maze task, post-training administration of cholinergic agonist, oxotremorine (0.1 mg/kg), improved the spatial learning deficit induced by mitragynine (5 and 10 mg/kg). The administration of physostigmine (0.1 mg/kg), an anticholinesterase only reversed the impairing effects of mitragynine on spatial learning at 5 mg /kg but not at higher dose (10 mg/kg). These results may indicate that mitragynine-induced spatial learning deficit is correlated with the depletion of acetylcholine level in memory-associated brain regions. Pre-treatment of mitragynine for 12 consecutive days led to differential cholinesterase activities in brain. No difference in acetylcholinesterase (AChE) activity was observed in frontal cortex. Remaining cortex which consists of major cortical tissues showed a decrease whilst hippocampus showed enhanced AChE activity in mitragynine-treated group at 10 mg/kg. Taken together, it can be concluded that mitragynine consumption can affect learning and memory functions as shown by the impaired behavioural performances and changes in brain activity.
Description
Keywords
Mitragyna speciosa Korth