Manvich Daniel F, Stowe Taylor A, Godfrey Jodi R, Weinshenker David
Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, Georgia.
Neuroscience and Behavioral Biology Program, Emory University, Atlanta, Georgia.
Biol Psychiatry. 2016 Jun 1;79(11):940-6. doi: 10.1016/j.biopsych.2015.07.002. Epub 2015 Jul 8.
We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event. After extinction training, reinstatement was assessed following re-exposure to these discrete cues. Animals re-exposed to psychosocial stress-predictive cues exhibited increased serum corticosterone and significantly greater reinstatement of cocaine seeking than the control group, and active coping behaviors during social defeat episodes were associated with subsequent reinstatement magnitude. These studies are the first to describe an operant model of psychosocial stress-induced relapse in rodents and lay the foundation for future work investigating its neurobiological underpinnings.
我们描述了一种在大鼠中使用社会挫败应激建立的应激诱导可卡因复吸的新型临床前模型，社会挫败应激是啮齿动物中一种符合行为学的社会心理应激源，与促进人类渴望和复吸的应激源非常相似。大鼠自我给药可卡因20天。在第11、14、17和20天，实验结束后，动物接受社会挫败应激或无应激的对照条件，有离散的环境刺激信号提示即将发生的事件。在消退训练后，再次暴露于这些离散线索后评估复吸情况。再次暴露于社会心理应激预测线索的动物血清皮质酮增加，与对照组相比，可卡因寻求行为的复吸明显更多，并且社会挫败发作期间的主动应对行为与随后的复吸程度相关。这些研究首次描述了啮齿动物中社会心理应激诱导复吸的操作性模型，并为未来研究其神经生物学基础的工作奠定了基础。
