Department of Psychology, Simon Fraser University, Burnaby, BC, Canada.
PLoS One. 2013 Nov 29;8(11):e82381. doi: 10.1371/journal.pone.0082381. eCollection 2013.
Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment with the dopamine synthesis inhibitor α-methylparatyrosine (AMPT). By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime) induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats.
昼夜节律活动节律受下丘脑视交叉上核（SCN）中的主起搏器和位于其他地方的食物可诱导的昼夜节律振荡器（FEOs）共同控制。SCN 介导与每日光暗周期的同步，而 FEOs 产生与定期每日进餐时间同步的活动节律。产生食物预期节律的 FEOs 的位置和使这些 FEOs 同步的途径仍有待阐明。为了深入了解同步途径，我们开发了一种测量药物探针对预期活动节律相位偏移的方案。我们使用该方案研究了多巴胺信号在昼夜食物预期时间安排中的作用。为了产生稳定的食物预期节律，大鼠每天进食 3 小时，从光照后 6 小时开始，或在持续光照下至少 3 周。然后，大鼠接受 D2 激动剂喹吡罗（1mg/kg IP）单独或在用多巴胺合成抑制剂α-甲基对酪氨酸（AMPT）预处理后接受。与载体注射相比，在熄灯前 1 小时（在下一餐前 19 小时）给予喹吡罗会导致活动起始的相位延迟，早于下一顿饭。在接受 AMPT 预处理的大鼠中，延迟变化更大，而在光照后 4 小时给予喹吡罗时则更小。在响应 D1 激动剂 SKF81297 时未观察到明显的变化。这些结果提供了证据，表明 D2 受体信号参与了负责大鼠昼夜食物预期节律的 FEOs 的相位控制。
