Circadian disruption causes deficits in attention and response inhibition in adult Long-Evans rats

Circadian rhythms are endogenous rhythms governing behavior and physiology. Circadian disruption is an environmental factor that impacts cognition and increases the risk of neurodegenerative disease by altering the circadian clock at a molecular level. Conventional sources of circadian disruption in human populations include working beyond the regular hours of ‘9 to 5’ (shift work) and untimely exposure to light (light-at-night, LAN). Our study investigated the effects of 2 models of circadian disruption on response inhibition, which has previously been unaddressed, and attention using a 5-choice serial reaction time task (5-CSRTT). Adult Long-Evans rats of both sexes were maintained on a 12h:12h light:dark cycle and tested under 3 conditions: 4 h into the dark phase with no exposure to ambient light at the time of testing (control), 4 h into the dark phase with exposure to ambient light during testing (a model of LAN), and 4 h into the light phase (a model of shift work). Our hypothesis that rats tested under both models of circadian disruption would have reduced response inhibition and attention versus controls was confirmed. We also established that changes in expression occur in Per2 in light phase models of circadian disruption. Chat and Drd1 showed rhythmic expression with peak expression during the dark phase. Because acetylcholine (ACh) governs circadian rhythms and attention, and DA modulates response inhibition, we performed drug challenges to examine for an interaction between the 2 neurotransmitter systems in our models. We combined an ACh agonist (nicotine) with antagonists for DA receptor 1 (SCH 23390) and DA receptor 2 (eticlopride) under the 3 circadian conditions to identify differential drug responses between treatment groups. The 2 circadian disruption models showed increased sensitivity to nicotine compared to control. SCH 23390 ameliorated the effect of nicotine in both models. This response to the combination of drugs confirms an interaction between cholinergic and dopaminergic neurotransmitters and identifies novel effects of circadian disruption on response to drugs. These results could potentially hold the key to better understanding altered cognitive functioning in real-world scenarios caused by conventional sources of circadian disruption