Endogenous circadian rhythms govern behavior and physiology, while circadian disruption is an environmental factor that impacts cognition by altering the circadian clock at a molecular level. We modeled the effects of 2 sources of circadian disruption – activity occurring during typical rest periods and untimely light exposure – to evaluate the effects of circadian disruption on behavior and underlying neurochemistry. Firstly, adult Long-Evans rats of both sexes were maintained on a 12 h:12 h light:dark cycle and tested using a 5-choice serial reaction time task (5-CSRTT) under 3 conditions: 4 h into the dark phase with no exposure to ambient light during testing (control), 4 h into the dark phase with exposure to ambient light during testing, and 4 h into the light phase. Both models resulted in impulsive behavior and reduced attention compared to control. We established that changes in the diurnal expression pattern occur in the clock gene Period 2 (Per2) in the light phase-tested model. Choline acetyltransferase (Chat) and Dopamine receptor 1 (Drd1) showed rhythmic expression with peak expression during the dark phase regardless of light-testing condition. Next, we performed drug challenges in a new rat cohort to examine the interaction between the cholinergic and dopaminergic neurotransmitter systems in regulating the behavioral changes caused by circadian disruption. We administered the cholinergic agonist nicotine and either the dopamine-1 receptor (DR1) antagonist SCH23390 or the DR2 antagonist eticlopride under the 3 circadian conditions to identify differential drug responses between treatment groups. Rats in both models demonstrated increased sensitivity to nicotine as compared to control, while SCH23390 and eticlopride ameliorated the effect of nicotine on 5-CSRTT performance in both models. Our study is the first to identify detrimental effects of both models of circadian disruption on impulsive behavior, and that the effects of circadian disruption are mediated by an interaction between cholinergic and dopaminergic systems.

内源性昼夜节律控制行为和生理，而昼夜节律紊乱是通过在分子水平上改变昼夜节律来影响认知的环境因素。我们对两种昼夜节律干扰源的影响进行了建模-正常休息期间发生的活动和不适当的光照-评估了昼夜节律干扰对行为和潜在神经化学的影响。首先，将成年的两性成年Long-Evans大鼠维持在12小时：12小时的光照：黑暗周期，并在以下3种条件下使用5选择序列反应时间任务（5-CSRTT）进行测试：4小时进入黑暗阶段，在测试（对照）过程中不暴露于环境光，在测试期间暴露于环境光中进入黑暗阶段4小时，在光照阶段暴露4小时。与对照相比，这两种模型均导致冲动行为并降低了注意力。我们确定昼夜表达模式的变化发生在时钟基因Period 2（Per2）在经过轻相位测试的模型中。胆碱乙酰转移酶（Chat）和多巴胺受体1（Drd1）在黑暗阶段均表现出有节奏的表达，而无论光照测试条件如何，其表达均达到峰值。接下来，我们在一个新的大鼠队列中进行了药物挑战，以检查胆碱能和多巴胺能神经递质系统之间的相互作用，以调节由昼夜节律引起的行为变化。我们在3个昼夜节律条件下给予了胆碱能激动剂烟碱和多巴胺1受体（DR1）拮抗剂SCH23390或DR2拮抗剂依替普利，以鉴定治疗组之间的药物反应差异。与对照相比，两种模型的大鼠均表现出对尼古丁的敏感性提高，而SCH23390和依替普利特改善了两种模型中尼古丁对5-CSRTT性能的影响。