Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Addict Biol. 2022 Mar;27(2):e13134. doi: 10.1111/adb.13134.
Traumatic brain injury (TBI) and drug addiction are common comorbidities, but it is unknown if the neurological sequelae of TBI contribute to this relationship. We have previously reported elevated oxycodone seeking after drug self-administration in rats that received repeated blast TBI (rbTBI). TBI and exposure to drugs of abuse can each change structural and functional neuroimaging outcomes, but it is unknown if there are interactive effects of injury and drug exposure. To determine the effects of TBI and oxycodone exposure, we subjected rats to rbTBI and oxycodone self-administration and measured drug seeking and several neuroimaging measures. We found interactive effects of rbTBI and oxycodone on fractional anisotropy (FA) in the nucleus accumbens (NAc) and that FA in the medial prefrontal cortex (mPFC) was correlated with drug seeking. We also found an interactive effect of injury and drug on widespread functional connectivity and regional homogeneity of the blood oxygen level dependent (BOLD) response, and that intra-hemispheric functional connectivity in the infralimbic medial prefrontal cortex positively correlated with drug seeking. In conclusion, rbTBI and oxycodone self-administration had interactive effects on structural and functional magnetic resonance imaging (MRI) measures, and correlational effects were found between some of these measures and drug seeking. These data support the hypothesis that TBI and opioid exposure produce neuroadaptations that contribute to addiction liability.
创伤性脑损伤 (TBI) 和药物成瘾是常见的共病,但尚不清楚 TBI 的神经后遗症是否促成了这种关系。我们之前曾报道过,在接受重复爆震性 TBI (rbTBI) 的大鼠中,阿片类药物自我给药后阿片类药物的渴望会增加。TBI 和滥用药物的暴露都可以改变结构和功能神经影像学结果,但尚不清楚损伤和药物暴露是否存在相互作用。为了确定 TBI 和阿片类药物暴露的影响,我们使大鼠接受 rbTBI 和阿片类药物自我给药,并测量药物寻求和几种神经影像学测量。我们发现 rbTBI 和阿片类药物对伏隔核 (NAc) 中各向异性分数 (FA) 有相互作用,并且内侧前额叶皮层 (mPFC) 中的 FA 与药物寻求呈正相关。我们还发现损伤和药物对血氧水平依赖 (BOLD) 反应的广泛功能连接和局部一致性有交互作用,并且边缘下内侧前额叶皮层的半球内功能连接与药物寻求呈正相关。总之,rbTBI 和阿片类药物自我给药对结构和功能磁共振成像 (MRI) 测量有相互作用,并且这些测量中的一些与药物寻求之间存在相关性。这些数据支持 TBI 和阿片类药物暴露产生神经适应,从而导致成瘾易感性的假设。