Drexel University College of Medicine, Department of Neurobiology and Anatomy, 2900 W Queen Lane, Philadelphia PA, 19129, United States.
Drexel University, A.J. Drexel Autism Institute, 3141 Chestnut Street, Philadelphia, PA 19104, United States.
Neuropharmacology. 2017 Oct;125:295-307. doi: 10.1016/j.neuropharm.2017.07.032. Epub 2017 Aug 1.
Patients with post-traumatic stress disorder have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We used the predator odor stress model of post-traumatic stress disorder with segregation of subjects as susceptible or resilient based on elevated plus maze behavior and context avoidance. We then determined behavioral and neurochemical differences across susceptible, resilient, and control populations using a panel of behavioral and neurochemical assays. Susceptible subjects showed a significant increase in the motoric and dopaminergic effects of cocaine, and this corresponded with heightened motivation to self-administer cocaine. Resilient subjects did not show differences in the motoric effects of cocaine, in dopamine signaling in vivo, or in any measure of cocaine self-administration. Nonetheless, we found that these animals displayed elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity ex vivo. Our results suggest that the experience of traumatic stress may produce alterations in dopamine systems that drive elevations in cocaine self-administration behavior in susceptible subjects, but may also produce both active and passive forms of resilience that function to prevent gross changes in cocaine's reinforcing efficacy in resilient subjects.
创伤后应激障碍患者易患物质使用障碍;然而,这种易感性的生物学基础仍未得到解决。我们使用创伤后应激障碍的捕食者气味应激模型,根据高架十字迷宫行为和情境回避将受试者分为易感或弹性组。然后,我们使用一系列行为和神经化学测定法,确定易感、弹性和对照人群之间的行为和神经化学差异。易感组的可卡因运动和多巴胺能作用显著增加,这与可卡因自我给药的动机增强相对应。弹性组在可卡因的运动效应、体内多巴胺信号或可卡因自我给药的任何测量中均未显示差异。尽管如此,我们发现这些动物在可卡因促进多巴胺释放的作用以及多巴胺自身受体敏感性方面均表现出升高。我们的结果表明,创伤应激的经历可能会导致多巴胺系统发生改变,从而导致易感组可卡因自我给药行为升高,但也可能产生主动和被动的弹性形式,以防止在弹性组中可卡因的强化效力发生明显变化。