Vivanco P, Studholme K M, Morin L P
Department of Psychiatry, Health Science Center, Stony Brook University, Stony Brook, NY, United States.
Neuroscience. 2013 Dec 19;254:98-109. doi: 10.1016/j.neuroscience.2013.09.025. Epub 2013 Sep 19.
Exposure of mice to a brief light stimulus during their nocturnal active phase induces several simultaneous behavioral or physiological responses, including circadian rhythm phase shifts, a drop in core body temperature (Tc), suppression of locomotor activity and sleep. Each response is triggered by light, endures for a relatively fixed interval and does not require additional light for expression. The present studies address the ability of the psychostimulant drugs, methamphetamine (MA), modafinil (MOD) or caffeine (CAF), to modify the light-induced responses. Drug or vehicle (VEH) was injected at CT11 into constant dark-housed mice then exposed to 5-min 100μW/cm(2) light or no light at CT13. Controls (VEH/Light) showed approximately 60-min phase delays. In contrast, response was substantially attenuated by each drug (only 12-15min delays). Under a 12-h light:12-h dark (LD12:12) photoperiod, VEH/light-treated mice experienced a Tc drop of about 1.3°C coincident with locomotor suppression and both effects were abolished by drug pre-treatment. Each drug elevated activity during the post-injection interval, but there was also evidence for CAF-induced hypoactivity in the dark prior to the photic test stimulus. CAF acutely elevated Tc; MA acutely lowered it, but both drugs reduced Tc during the early dark (ZT12.5-ZT13). The ability of the psychostimulant drugs to block the several effects of light exposure is not the result of drug-induced hyperactivity. The results raise questions concerning the manner in which drugs, activity, sleep and Tc influence behavioral and physiological responses to light.
在夜间活动期让小鼠短暂暴露于光刺激下会引发几种同时出现的行为或生理反应,包括昼夜节律相位偏移、核心体温(Tc)下降、运动活动抑制和睡眠。每种反应均由光触发,持续一段相对固定的时间间隔,且表达时不需要额外的光。本研究探讨了精神兴奋药物甲基苯丙胺(MA)、莫达非尼(MOD)或咖啡因(CAF)改变光诱导反应的能力。在CT11给持续饲养在黑暗中的小鼠注射药物或赋形剂(VEH),然后在CT13让其暴露于5分钟100μW/cm²的光下或不暴露于光。对照组(VEH/光)显示出约60分钟的相位延迟。相比之下,每种药物都使反应显著减弱(仅12 - 15分钟延迟)。在12小时光照:12小时黑暗(LD12:12)光周期下,VEH/光处理的小鼠出现约1.3°C的Tc下降,同时伴有运动抑制,药物预处理消除了这两种效应。每种药物在注射后间隔期均提高了活动量,但也有证据表明在光测试刺激前黑暗中CAF诱导了活动减少。CAF使Tc急性升高;MA使其急性降低,但两种药物在早期黑暗(ZT12.5 - ZT13)期间均降低了Tc。精神兴奋药物阻断光暴露的几种效应的能力并非药物诱导的多动所致。这些结果引发了关于药物、活动、睡眠和Tc影响对光的行为和生理反应方式的问题。