Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06519, USA.
Sci Rep. 2023 May 9;13(1):7507. doi: 10.1038/s41598-023-33458-8.
Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.
阿片类药物被用于缓解疼痛已有数千年的历史，但它们具有很大的滥用潜力。处方类阿片类药物，如羟考酮，与 32%的过量用药有关，在 2021 年导致了总共 75673 例死亡。一个主要的挑战是最大限度地发挥其治疗潜力，同时最大限度地减少包括阿片类药物使用障碍（OUD）在内的负面副作用。生酮饮食（KD）已被报道能减轻疼痛和减少酒精使用障碍的严重程度，但它对羟考酮反应的影响尚不清楚。KD 小鼠表现出羟考酮诱导的运动活性增加和羟考酮的镇痛作用增强，表明饮食对阿片类药物敏感性有影响。暴露于慢性羟考酮的雄性 KD 小鼠表现出纳洛酮诱导的跳跃增加，表明饮食对阿片类药物戒断有性别特异性影响。与此一致的是，雄性 KD 小鼠自我给予的羟考酮较少，而雌性 KD 小鼠与对照组没有差异。最后，在渐进比例时间表中，KD 对获得羟考酮的动机没有影响。这些数据表明 KD 对阿片类药物反应的性别偏倚影响，在临床疼痛管理和治疗 OUD 中应考虑并可能利用这些影响。
