Pitcairn Stacy R, Ortelli Olivia A, Weiner Jeffrey L
Department of Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Alcohol Clin Exp Res (Hoboken). 2024 Aug;48(8):1586-1599. doi: 10.1111/acer.15397. Epub 2024 Jun 20.
Exposure to stress during childhood and adolescence is a risk factor for alcohol use disorder (AUD) and comorbid conditions, including posttraumatic stress disorder (PTSD). We previously established an adolescent social isolation (SI) model that leads to the emergence of a wide range of behavioral risk factors for AUD, including increased anxiety-like behavior, locomotor activity, and ethanol consumption in male and female rats. Here, we sought to test the hypothesis that SI may increase vulnerability to single prolonged stress (SPS), a rodent model of PTSD.
Female Long Evans rats (n = 8/group) were either single-housed or group-housed (GH) (4/cage) on postnatal day 21. One week later, rats underwent testing in the open field test (OFT), elevated plus-maze (EPM), and successive alleys test (SAT). Following initial behavioral testing, a subset of SI/GH rats were exposed to SPS. All rats were then tested on the novelty-suppressed feeding test (NSFT) followed by fear conditioning and home cage two-bottle choice to assess ethanol consumption.
SI significantly increased activity in the OFT and anxiety-like behavior on the SAT, but not the EPM. While SI and SPS alone had no effect on the NSFT, exposure to both stressors significantly increased approach latency. Complex effects of stress history were observed across a 3-day fear conditioning paradigm and no group differences were observed with home cage ethanol consumption, regardless of prior ethanol exposure.
The results from this study provide novel evidence that SI interacts with SPS in female rats to influence behavior in assays of unconditioned anxiety-like behavior (NSFT) and conditioned fear. Surprisingly, stress exposure had no effect on home cage ethanol consumption. Ultimately, these models provide useful avenues to examine the interaction between stressful experiences, alcohol exposure, biological sex, and the neurobiological adaptations underlying potential risk factors for psychiatric conditions.
童年和青少年时期暴露于压力之下是酒精使用障碍(AUD)及共病状况(包括创伤后应激障碍(PTSD))的一个风险因素。我们之前建立了一种青少年社会隔离(SI)模型,该模型导致出现了一系列AUD行为风险因素,包括雄性和雌性大鼠焦虑样行为增加、运动活动增加以及乙醇消耗量增加。在此,我们试图检验SI可能会增加对单次长时间应激(SPS)(一种PTSD啮齿动物模型)易感性的假说。
雌性Long Evans大鼠(每组n = 8只)在出生后第21天被单独饲养或群居(GH)(每笼4只)。一周后,大鼠在旷场试验(OFT)、高架十字迷宫(EPM)和连续小巷试验(SAT)中接受测试。在初始行为测试之后,一部分SI/GH大鼠接受SPS。然后所有大鼠在新奇抑制摄食试验(NSFT)中接受测试,随后进行恐惧条件反射和笼内双瓶选择以评估乙醇消耗量。
SI显著增加了OFT中的活动以及SAT中的焦虑样行为,但在EPM中未增加。虽然单独的SI和SPS对NSFT没有影响,但同时暴露于两种应激源会显著增加接近潜伏期。在为期3天的恐惧条件反射范式中观察到了应激史的复杂影响,并且无论之前是否接触过乙醇,笼内乙醇消耗量均未观察到组间差异。
本研究结果提供了新的证据,表明SI与雌性大鼠中的SPS相互作用,以影响非条件性焦虑样行为(NSFT)和条件性恐惧试验中的行为。令人惊讶的是,应激暴露对笼内乙醇消耗量没有影响。最终,这些模型为研究应激经历、酒精暴露、生物性别以及精神疾病潜在风险因素背后的神经生物学适应之间的相互作用提供了有用的途径。