Department of Neurosciences, (SLO, AZ, AA, KCC, JLB), University of New Mexico School of Medicine, Albuquerque, New Mexico.
New Mexico Alcohol Research Center, (SLO, AA, KCC, JLB), UNM Health Sciences Center, Albuquerque, New Mexico.
Alcohol Clin Exp Res. 2019 Sep;43(9):1949-1956. doi: 10.1111/acer.14149. Epub 2019 Aug 14.
Fetal alcohol spectrum disorders (FASD) commonly include deficits in learning, memory, and executive control that can have a severe negative impact on quality of life across the life span. It is still unclear how prenatal alcohol exposure (PAE) affects executive control processes, such as control over reward seeking, that lead to inappropriate behavior later in life. Learning and reinstatement of a previously learned response after extinction is a simple, well-validated measure of both acquisition of a rewarded instrumental response and sensitivity to reward and reward-associated cues. We investigated the effects of PAE on learning, extinction, and reinstatement of a simple instrumental response for food reward. Next, we assessed the effectiveness of an early intervention, communal nest (CN) housing, on increased reinstatement of an extinguished response seen after PAE.
To assess the effects of PAE on control over reward seeking, we tested male and female PAE and saccharine (SAC) controls raised in a standard nest (SN) on the acquisition, extinction, and food reward-induced reinstatement of an instrumental response utilizing a touch screen-based paradigm. Next, in order to examine the effects of an early-life intervention on these behaviors, we tested PAE and SAC mice raised in a CN early-life environment on these behaviors.
PAE mice readily acquired and extinguished a simple touch response to a white square stimulus. However, PAE mice showed significantly increased and persistent reinstatement compared to controls. Increased maternal care via rearing in CN slowed acquisition and sped extinction learning and rescued the significantly increased reinstatement responding in PAE mice.
Together these results demonstrate that even moderate PAE is sufficient to alter control over reward seeking as measured by reinstatement. Importantly, an early-life intervention previously shown to improve cognitive outcomes in PAE mice was sufficient to ameliorate this effect.
胎儿酒精谱系障碍(FASD)通常包括学习、记忆和执行控制方面的缺陷,这些缺陷会对整个生命周期的生活质量产生严重的负面影响。目前尚不清楚产前酒精暴露(PAE)如何影响执行控制过程,例如对奖励寻求的控制,这些控制会导致以后生活中的不当行为。学习和在消退后重新获得先前学习的反应是衡量获得奖励性工具反应以及对奖励和与奖励相关的线索的敏感性的一种简单、经过充分验证的方法。我们研究了 PAE 对食物奖励的简单工具反应的学习、消退和重新获得的影响。接下来,我们评估了早期干预措施,公共巢(CN)饲养,对 PAE 后观察到的已消退反应的重新获得的有效性。
为了评估 PAE 对奖励寻求控制的影响,我们使用基于触摸屏的范式,在标准巢(SN)中测试雄性和雌性 PAE 和蔗糖(SAC)对照动物,以评估 PAE 对奖励寻求控制的影响。控制获得、消退和食物奖励诱导的工具反应的重新获得。接下来,为了研究早期生活干预对这些行为的影响,我们在 CN 早期生活环境中测试了 PAE 和 SAC 小鼠,以研究这些行为。
PAE 小鼠很容易获得并消除对白色正方形刺激的简单触摸反应。然而,PAE 小鼠的重新获得明显增加且持续时间延长,与对照组相比。通过在 CN 中饲养增加的母体照顾会减缓获得速度,加快消退学习速度,并挽救 PAE 小鼠中明显增加的重新获得反应。
这些结果表明,即使是中度 PAE 也足以改变通过重新获得来衡量的奖励寻求控制。重要的是,以前被证明可以改善 PAE 小鼠认知结果的早期生活干预措施足以改善这种效果。