Department of Neuroscience, Oberlin College, Oberlin, OH, 44074, United States.
Department of Neuroscience, Oberlin College, Oberlin, OH, 44074, United States.
Behav Brain Res. 2021 Sep 24;414:113488. doi: 10.1016/j.bbr.2021.113488. Epub 2021 Jul 28.
In humans, adverse childhood experiences are associated with an increased risk of developing a neuropsychiatric disorder. Changes in social behavior and cognitive function are hallmarks of numerous neuropsychiatric disorders. Here we examined the effects of exposure to variable stress during the juvenile period on social behavior, reward, and cognitive function (as measured in the 5-choice serial reaction time task (5CSRTT)) in rats. From postnatal days (PND) 25-29 male and female rats were exposed to a variable stress protocol. In adulthood, social interactions and sucrose preference were assessed prior to training on the 5CSRTT. Once successfully trained, rats were challenged with different task versions, and then the effects of cocaine (0, 10, or 20 mg/kg, IP) on performance were assessed. A follow-up experiment examined the ability of the D2 receptor antagonist eticlopride (0.0, 0.025, 0.05 mg/kg, IP) to block the effects of cocaine on 5CSRTT performance in female rats. Male rats exposed to juvenile stress tended to engage in less social behavior and had an increased correct response latency in the 5CSRTT following cocaine administration. Female rats exposed to juvenile stress exhibited a trend towards increased social behavior and demonstrated increased cocaine-induced impulsivity. The increase in impulsivity was not blocked by co-administration of eticlopride. Juvenile stress had minimal effects on adult behavior in male rats, but increased cocaine-induced impulsivity in female rats. Such an effect could contribute to the enhanced escalation of drug-use observed in females that experience juvenile stress. This possibility awaits further testing.
在人类中，不良的童年经历与神经精神障碍的发病风险增加有关。社会行为和认知功能的改变是许多神经精神障碍的标志。在这里，我们研究了幼年时期暴露于可变应激对大鼠社会行为、奖励和认知功能（如 5 选择连续反应时间任务（5CSRTT）测量）的影响。从出生后第 25-29 天起，雄性和雌性大鼠接受可变应激方案。在成年期，在进行 5CSRTT 训练之前，评估社交互动和蔗糖偏好。一旦成功训练，用不同的任务版本对大鼠进行挑战，然后评估可卡因（0、10 或 20mg/kg，IP）对表现的影响。后续实验研究了 D2 受体拮抗剂 eticlopride（0.0、0.025、0.05mg/kg，IP）阻断可卡因对雌性大鼠 5CSRTT 表现的影响的能力。暴露于幼年应激的雄性大鼠表现出较少的社交行为倾向，并且在可卡因给药后在 5CSRTT 中的正确反应潜伏期增加。暴露于幼年应激的雌性大鼠表现出社交行为增加的趋势，并表现出可卡因诱导的冲动性增加。可卡因诱导的冲动性增加不能通过共同给予 eticlopride 来阻断。幼年应激对雄性大鼠成年行为的影响很小，但增加了雌性大鼠可卡因诱导的冲动性。这种影响可能导致经历幼年应激的女性中观察到的药物使用增加的加剧。这一可能性有待进一步检验。
