Opiol Hanna, de Zavalia Nuria, Delorme Tara, Solis Pavel, Rutherford Spencer, Shalev Uri, Amir Shimon
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, QC, Canada.
PLoS One. 2017 Mar 16;12(3):e0174113. doi: 10.1371/journal.pone.0174113. eCollection 2017.
Food entrainment is the internal mechanism whereby the phase and period of circadian clock genes comes under the control of daily scheduled food availability. Food entrainment allows the body to efficiently realign the internal timing of behavioral and physiological functions such that they anticipate food intake. Food entrainment can occur with or without caloric restriction, as seen with daily schedules of restricted feeding (RF) or restricted treat (RT) that restrict food or treat intake to a single feeding time. However, the extent of clock gene control is more pronounced with caloric restriction, highlighting the role of energy balance in regulating clock genes. Recent studies have implicated dopamine (DA) to be involved in food entrainment and caloric restriction is known to affect dopaminergic pathways to enhance locomotor activity. Since food entrainment results in the development of a distinct behavioral component, called food anticipatory activity (FAA), we examined the role of locomotor sensitization (LS) in food entrainment by 1) observing whether amphetamine (AMPH) sensitization results in enhanced locomotor output of FAA and 2) measuring LS of circadian and non-circadian feeding paradigms to an acute injection of AMPH (AMPH cross-sensitization). Unexpectedly, AMPH sensitization did not show enhancement of FAA. On the contrary, LS did develop with sufficient exposure to RF. LS was present after 2 weeks of RF, but not after 1, 3 or 7 days into RF. When food was returned and rats regain their original body weight at 10-15 days post-RF, LS remained present. LS did not develop to RT, nor to feedings of a non-circadian schedule, e.g. variable restricted feeding (VRF) or variable RT (VRT). Further, when RF was timed to the dark period, LS was observed only when tested at night; RF timed to the light period resulted in LS that was present during day and night. Taken together our results show that LS develops with food entrainment to RF, an effect that is dependent on the chronicity and circadian phase of RF but independent of body weight. Given that LS involves reorganization of DA-regulated motor circuitry, our work provides indirect support for the role of DA in the food entrainment pathway of RF. The findings also suggest differences in neuronal pathways involved in LS from AMPH sensitization and LS from RF.
食物诱导是一种内在机制，通过该机制，昼夜节律时钟基因的相位和周期受到每日定时食物供应的控制。食物诱导使身体能够有效地重新调整行为和生理功能的内部时间，以便它们能够预期食物摄入。无论有无热量限制，食物诱导都可能发生，如在限制进食（RF）或限制零食（RT）的日常安排中，将食物或零食摄入限制在单一进食时间。然而，热量限制对时钟基因的控制程度更为显著，突出了能量平衡在调节时钟基因中的作用。最近的研究表明多巴胺（DA）参与食物诱导，并且已知热量限制会影响多巴胺能通路以增强运动活动。由于食物诱导会导致一种独特行为成分的形成，称为食物预期活动（FAA），我们通过以下方式研究了运动敏化（LS）在食物诱导中的作用：1）观察安非他明（AMPH）敏化是否会导致FAA的运动输出增强；2）测量昼夜节律和非昼夜节律进食模式对急性注射AMPH的运动敏化（AMPH交叉敏化）。出乎意料的是，AMPH敏化并未显示FAA增强。相反，通过充分暴露于RF确实会产生LS。RF持续两周后会出现LS，但在RF的第1、3或7天之后不会出现。当食物恢复供应且大鼠在RF后10 - 15天恢复到原始体重时，LS仍然存在。LS不会因RT产生，也不会因非昼夜节律的进食安排产生，例如可变限制进食（VRF）或可变RT（VRT）。此外，当RF安排在黑暗期时，仅在夜间测试时才观察到LS；RF安排在光照期会导致昼夜均出现LS。综合我们的结果表明，LS随着对RF的食物诱导而产生，这种效应取决于RF的持续性和昼夜节律相位，但与体重无关。鉴于LS涉及DA调节的运动回路的重组，我们的工作为DA在RF的食物诱导途径中的作用提供了间接支持。这些发现还表明，参与LS的神经元通路与AMPH敏化引起的LS以及RF引起的LS存在差异。
