Hofford Rebecca S, Prendergast Mark A, Bardo Michael T
Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA.
Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA.
Behav Brain Res. 2018 Feb 15;338:143-152. doi: 10.1016/j.bbr.2017.10.023. Epub 2017 Oct 20.
Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration.
直到最近，用于研究创伤后应激障碍（PTSD）与药物使用之间相互作用的啮齿动物模型还很少。与PTSD一样，单次长时间应激（SPS）会导致下丘脑-垂体-肾上腺（HPA）轴功能障碍，并改变精神兴奋剂的自我给药行为。其他应激源，如隔离应激，也会改变精神兴奋剂的自我给药行为。然而，目前尚不清楚隔离饲养与SPS相结合是否会改变可卡因自我给药行为的习得或维持。本研究对处于隔离条件（Iso）、丰富条件（Enr）或标准条件（Std）下饲养的大鼠施加改良的SPS（modSPS；两小时束缚后紧接着冷水游泳应激），以测量可卡因自我给药行为和HPA标志物的变化。无论饲养条件如何，与未受应激的对照组相比，暴露于modSPS的大鼠在初始习得期间皮质酮（CORT）释放量更高，可卡因自我给药量减少。此外，在初始习得期间，与暴露于modSPS的Enr和Std大鼠相比，接受Iso饲养和modSPS的大鼠在各实验阶段可卡因自我给药量的增加更为迅速。初始习得后，剂量反应分析表明，Iso大鼠总体上对可卡因单位剂量的变化最为敏感；然而，modSPS对可卡因剂量反应曲线没有影响。此外，modSPS或不同饲养方式对下丘脑、内侧前额叶皮质、杏仁核或伏隔核中糖皮质激素受体（GR）的表达均无影响。通过将modSPS与Iso饲养相结合，本研究确定了每种应激源对可卡因自我给药行为习得的独特作用。
