Drugs that prevent mouse sleep also block light-induced locomotor suppression, circadian rhythm phase shifts and the drop in core temperature

- Three stimulant drugs are tested for their effects on responses to light.
- Methamphetamine, modafinil and caffeine pre-treatment block responses to light.
- Phase shifts, activity suppression and the drop in core temperature are blocked.
- Response blockade can occur without drug-induced activity increases.
- Light may modulate all three responses via a common input pathway.

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 100 μW/cm2 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 12-15 min 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.