Department of Psychology, Barnard College, New York, NY 10027.
Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz 91190, México.
eNeuro. 2018 Apr 6;5(2). doi: 10.1523/ENEURO.0433-17.2018. eCollection 2018 Mar-Apr.
The ability to sense time and anticipate events is critical for survival. Learned responses that allow anticipation of the availability of food or water have been intensively studied. While anticipatory behaviors also occur prior to availability of regularly available rewards, there has been relatively little work on anticipation of drugs of abuse, specifically methamphetamine (MA). In the present study, we used a protocol that avoided possible CNS effects of stresses of handling or surgery by testing anticipation of MA availability in animals living in their home cages, with daily voluntary access to the drug at a fixed time of day. Anticipation was operationalized as the amount of wheel running prior to MA availability. Mice were divided into four groups given access to either nebulized MA or water, in early or late day. Animals with access to MA, but not water controls, showed anticipatory activity, with more anticipation in early compared to late day and significant interaction effects. Next, we explored the neural basis of the MA anticipation, using c-FOS expression, in animals euthanized at the usual time of nebulization access. In the dorsomedial hypothalamus (DMH) and orbitofrontal cortex (OFC), the pattern of c-FOS expression paralleled that of anticipatory behavior, with significant main and interaction effects of treatment and time of day. The results for the lateral septum (LS) were significant for main effects and marginally significant for interaction effects. These studies suggest that anticipation of MA is associated with activation of brain regions important in circadian timing, emotional regulation, and decision making.
感知时间和预测事件的能力对生存至关重要。人们对能够预测食物或水供应的习得性反应进行了深入研究。虽然在定期供应的奖励之前也会出现预期行为，但对于预测滥用药物（例如甲基苯丙胺，即 MA）的研究相对较少。在本研究中，我们使用了一种方案，通过在动物的家中笼子中测试 MA 可用性之前避免处理或手术引起的中枢神经系统压力的可能影响，每天在固定时间让动物自由地接触药物。预期通过 MA 可用性之前的轮跑量来实现。将小鼠分为四组，分别给予雾化 MA 或水，分为早组或晚组。有 MA 但没有水对照组的动物表现出预期活动，与晚组相比，早组的预期更多，并且有显著的交互作用。接下来，我们使用 c-FOS 表达，在通常雾化接触时处死动物，探索 MA 预期的神经基础。在背内侧下丘脑（DMH）和眶额皮质（OFC）中，c-FOS 表达的模式与预期行为相似，具有治疗和时间的显著主效应和交互作用。外侧隔核（LS）的结果仅具有主效应显著，交互效应具有边缘显著。这些研究表明，MA 的预期与参与生物钟、情绪调节和决策的大脑区域的激活有关。
