Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Addict Biol. 2012 Sep;17(5):920-33. doi: 10.1111/j.1369-1600.2012.00460.x. Epub 2012 Jun 28.
Stressful experiences can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock (stress history) or light cues alone (control) prior to acquisition of alcohol self-administration (1-hour sessions, fixed ratio 1-3, 100 µl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a twofold elevation in alcohol self-administration, as compared with low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate and cyclic guanosine monophosphate hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low-drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals.
应激体验可导致饮酒增加，例如许多创伤后应激障碍患者。然而，应激史而非急性应激源如何影响饮酒量尚不清楚。为了模拟过去应激的长期影响，雄性 Wistar 大鼠在获得酒精自我给药之前（1 小时期，固定比率 1-3，作为强化物的 10% v/v 酒精 100µl）接受光提示的足底电击（应激史）或仅光提示（对照）。应激史并未改变自我给药获得期间的平均酒精摄入量，但增加了对酒精配对杠杆的偏好超过非活动杠杆。在消退期后，与无应激史的低饮酒量大鼠相比，经历过应激暴露和低基线酒精摄入的大鼠的酒精自我给药量增加了两倍。在自我给予 0.1%蔗糖的大鼠中没有观察到类似的效果。磷酸二酯酶 10A（PDE10A）的 mRNA 水平分析，一种双特异性环腺苷单磷酸和环鸟苷单磷酸水解酶，显示应激史增加了外侧杏仁核中的 Pde10a mRNA 水平，并且在低饮酒量大鼠中，前额叶皮层的前扣带回（plPFC）。plPFC 中的 Pde10a mRNA 水平与复发样阶段期间更大的酒精自我给药直接相关，而 BLA 中的 Pde10a mRNA 水平与获得后乙醇偏好增加相关。数据表明，应激史使原本低饮酒量的大鼠在类似复发的情况下更容易饮酒，并确定了杏仁核和前额叶皮层 PDE10A 表达中的应激诱导的神经适应性改变，这些改变可能导致易感个体的酒精摄入量和偏好增加。
