背景:阿片类药物成瘾的治疗是一种未满足的医疗需求。反复接触阿片类药物会破坏认知表现。阿片类药物替代疗法,with,例如,美沙酮,可能会进一步加剧认知缺陷。越来越多的证据表明mitragynine,来自Kratom(Mitragynaspeciosa)叶子的主要生物碱,可能是鸦片成瘾的有希望的替代疗法。然而,对其健康后果的了解仍然有限。
目的:我们的目的是研究吗啡戒断大鼠的mitragynine替代的认知效应。此外,我们询问脑源性神经营养因子(BDNF)和Ca2+/钙调蛋白依赖性激酶IIα(αCaMKII)等神经元成瘾标志物是否可能介导观察到的效应.
方法:雄性Sprague-Dawley大鼠在停止治疗前给予递增剂量的吗啡以诱导自发的吗啡戒断。然后,媒介物或mitragynine(5mg/kg,15mg/kg,或30mg/kg)替换3天。媒介物处理组用作对照。戒断症状在24小时后进行评分,48h,和72小时,而在替代期间测试了新物体识别(NOR)和注意力集合转移(ASST)。
结果:在ASST中,停用吗啡显著诱导吗啡戒断体征和认知缺陷。用mitragynine代替能够减轻戒断症状。Mitragynine不会影响NOR的识别记忆,但会显着改善吗啡戒断大鼠的逆转学习缺陷。
结论:这些数据支持mitragynine可以作为安全的药物治疗来治疗阿片类药物成瘾,对认知缺陷有益。
BACKGROUND: The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g., methadone, may further exacerbate the cognitive deficits. Growing evidence suggests that mitragynine, the primary alkaloid from the Kratom (Mitragyna speciosa) leaves, may serve as a promising alternative therapy for opiate addiction. However, the knowledge of its health consequences is still limited.
OBJECTIVE: We aimed to examine the cognitive effects of mitragynine substitution in morphine-withdrawn rats. Furthermore, we asked whether neuronal addiction markers like the brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent kinase II alpha (αCaMKII) might mediate the observed effects.
METHODS: Male Sprague-Dawley rats were given morphine at escalating doses before treatment was discontinued to induce a spontaneous morphine withdrawal. Then, vehicle or mitragynine (5 mg/kg, 15 mg/kg, or 30 mg/kg) substitution was given for 3 days. A vehicle-treated group was used as a control. Withdrawal signs were scored after 24 h, 48 h, and 72 h, while novel object recognition (NOR) and attentional set-shifting (ASST) were tested during the substitution period.
RESULTS: Discontinuation of morphine significantly induced morphine withdrawal signs and cognitive deficit in the ASST. The substitution with mitragynine was able to alleviate the withdrawal signs. Mitragynine did not affect the recognition memory in the NOR but significantly improved the reversal learning deficit in the morphine-withdrawn rats.
CONCLUSIONS: These data support the idea that mitragynine could be used as safe medication therapy to treat opiate addiction with beneficial effects on cognitive deficits.