Programs in Neuroscience and Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology (VCAPP), 205 Wegner Hall, Washington State University, Pullman, WA 99164, USA.
Neuroscience. 2011 Mar 10;176:284-95. doi: 10.1016/j.neuroscience.2010.12.022. Epub 2010 Dec 24.
The rewarding influence of drugs of abuse varies with time of day and appears to involve interactions between the circadian and the mesocorticolimbic dopamine systems. The circadian system is also intimately involved in measuring daylength. Thus, the present study examined the impact of changing daylength (photoperiod) on cocaine-seeking behaviors. Male Sprague-Dawley rats were trained and tested on a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20) to determine a preference score. Rats were then shifted to either shorter (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re-tested for cocaine-induced reinstatement under each different condition, and then returned to their original photoperiod (12L:12D) and tested once more. Rats exhibited a circadian profile of preference score in constant darkness with a peak at 12 h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter photoperiods profoundly suppressed cocaine reinstatement, which did not recover even after switching back to 12L:12D. In contrast, longer photoperiods did not alter reinstatement. Separate studies showed that the suppression of cocaine reinstatement was not due to repeated testing. In an additional experiment, we examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) proteins in drug-naive rats. These results revealed photoperiodic modulation of proteins in the prefrontal cortex and dorsal striatum, but not in the nucleus accumbens or ventral tegmental area. Together, these findings add further support to the circadian genesis of cocaine-seeking behaviors and demonstrate that drug-induced reinstatement is modulated by photoperiod. Furthermore, the results suggest that photoperiod partly contributes to the seasonal expression of certain drug-related behaviors in humans living at different latitudes and thus our findings may have implications for novel targeting of circadian rhythms in the treatment of addiction.
药物滥用的奖励影响随时间而变化，似乎涉及昼夜节律和中脑边缘多巴胺系统之间的相互作用。昼夜节律系统也密切参与测量日照时间。因此，本研究探讨了改变日照时间（光周期）对可卡因觅药行为的影响。雄性 Sprague-Dawley 大鼠在 12L:12D 光照：黑暗时间表上接受训练和测试，以在一天中的三个时间（ Zeitgeber 时间（ZT）：4、12 和 20）进行可卡因诱导的条件性位置偏好（CPP）复燃，以确定偏好分数。然后，大鼠被转移到较短（6L:18D）或较长（18L:6D）的光周期，然后转移到恒定条件下，在每种不同条件下重新测试可卡因诱导的复燃，然后返回其原始光周期（12L:12D）并再次测试。大鼠在持续黑暗中表现出昼夜节律偏好评分模式，在熄灯后 12 小时达到峰值。在 ZT4 和 ZT20，但不在 ZT12，较短的光周期会强烈抑制可卡因复燃，即使切换回 12L:12D 也不会恢复。相比之下，较长的光周期不会改变复燃。单独的研究表明，可卡因复燃的抑制不是由于重复测试。在另一个实验中，我们检查了酪氨酸羟化酶（TH）和多巴胺转运蛋白（DAT）蛋白在药物-naive 大鼠中的光周期调节。这些结果显示了前额叶皮层和背侧纹状体中蛋白质的光周期调节，但在伏隔核或腹侧被盖区没有。总之，这些发现进一步支持了可卡因觅药行为的昼夜节律起源，并证明了药物诱导的复燃受光周期的调节。此外，研究结果表明，光周期部分导致了不同纬度生活的人类中某些与药物相关行为的季节性表达，因此我们的发现可能对治疗成瘾的昼夜节律靶向具有重要意义。
