眶额皮层和背侧纹状体的功能连接预测自愿戒毒后阿片类药物渴求的潜伏期。
Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence.
机构信息
Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/NIH, Baltimore, MD 21224.
Center for Social and Affective Neuroscience, Linköping University, Linköping 581 83, Sweden.
出版信息
Proc Natl Acad Sci U S A. 2021 Oct 26;118(43). doi: 10.1073/pnas.2106624118.
We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.
我们最近引入了一种大鼠模型，用于研究在药物寻找的负面后果引起的自愿戒断后，阿片类物质渴望的潜伏期。在这里，我们使用静息态功能磁共振成像来确定眶额皮层（OFC）回路的纵向功能连接变化是否预测自愿戒断后阿片类物质渴望的潜伏期。我们训练大鼠在 14 天内通过静脉注射羟考酮或美味食物进行自我给药。3 天后，我们引入了一个电子障碍，持续 12 天，导致奖励自我给药停止。我们在自我给药训练后（早期戒断）和电子障碍暴露后（晚期戒断）立即对大鼠进行羟考酮或食物寻找测试。我们在自我给药前和早期及晚期戒断期间对它们的大脑进行成像。我们分析了由奖励自我给药和电子障碍引起的戒断引起的 OFC 功能连接变化。晚期戒断时，羟考酮的寻找明显多于早期戒断（阿片类物质渴望的潜伏期）。羟考酮自我给药经验增加了 OFC 与背侧纹状体和相关回路的功能连接，与孵育的羟考酮寻找呈正相关。相比之下，电子障碍引起的戒断减少了 OFC 与背侧纹状体和相关回路的功能连接，与孵育的羟考酮寻找呈负相关。早期戒断时，食物的寻找明显多于晚期戒断（食物渴望的缓解）。食物自我给药经验和电子障碍引起的戒断减少或维持了这些回路中的功能连接，与缓解的食物寻找无关。阿片类药物自我给药与自愿戒断引起的 OFC 与背侧纹状体和相关回路的功能连接的相反变化预测了阿片类物质渴望潜伏期的个体差异。
Zotero 插件