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

Abstract

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.

Keywords: 12-h light:12-h dark; ANOVA; CAF; DA; DD; DMSO; DSI; Data Sciences International; IP; LD12:12; LED; MA; MOD; SCN; SNK; Student–Newman–Keuls; Tc; VEH; analysis of variance; arousal; caffeine; circadian; constant dark; core body temperature; dimethyl sulfoxide; dopamine; intraperitoneal; light emitting diodes; masking; methamphetamine; modafinil; photosomnolence; suprachiasmatic; suprachiasmatic nucleus; thermoregulation; vehicle.

Figure 1

Raster scan wheel running records of individual mice in DD which are pre-treated (arrowheads) with modafinil (MOD) or vehicle (VEH), then exposed to a 5 min pulse of Light or NoLight at CT13-CT14 (triangle). Only the VEH/Light mice had significant phase shifts (see text).

Figure 2

Light delivered at CT13-CT14 induces large phase delays (mean ± SEM) which are generally blocked by modafinil (MOD) pre-treatment. Black dots indicate data points of individuals and the number of animals per group is in parentheses. Significant pair-wise differences are indicated by p values (see text).

Figure 3

Light delivered at CT13-CT14 induces large phase delays (mean ± SEM) which are generally blocked by methamphetamine (MA) pre-treatment. Black dots indicate data points of individuals and the number of animals per group is in parentheses. Significant pair-wise comparisons are indicated by p values (see text).

Figure 4

Light delivered at CT13-CT14 induces large phase delays (mean ± SEM) which are generally blocked by 40 mg caffeine (CAF) pre-treatment. Black dots indicate data points of individuals and the number of animals per group is in parentheses. Significant pair-wise comparisons are indicated by p values (see text)..

Figure 5

Modafinil (MOD; Panel D) blocks both light-induced locomotor suppression and the associated Tc drop in vehicle-treated mice (Panel B; double-headed arrow). Arrowhead and dashed vertical line - time of VEH (panels A, B) or MOD injection (panels C, D); shaded area - early dark phase (ZT12-ZT14). The light pulse was administered for 5 min beginning at minute 0 (ZT13; hatched vertical bar, panels B,D). Dotted data line - Tc obtained with DSI transmitters; solid data line - DSI activity index. N=7/group.

Figure 6

Methamphetamine (MA; Panel D) blocks both light-induced locomotor suppression and the associated Tc drop in vehicle-treated mice (Panel B; double-headed arrow). Panel A - effect of VEH/noLight; Panel C - effect of MA/noLight. Arrowhead and dashed vertical line - approximate time of VEH (panels A,B) or MA injection (panels C,D); shaded area - early dark phase (ZT12-ZT14). The light pulse was administered for 5 min beginning at minute 0 (ZT13; hatched vertical bar, panels B,D). Dotted data line - Tc obtained with DSI transmitters ; solid data line - DSI activity index. N = 7/group.

Figure 7

Caffeine (CAF; 40 mg) treatment blocks (panel F) both light-induced locomotor suppression and the associated drop in Tc; 20 mg has a partial effect (panel D; double-ended arrows) compared to the effect of vehicle (VEH; panel B). Arrowhead and dashed vertical line - approximate time of VEH (panels A,B) or CAF (panels C-F) injection; shaded area - early dark phase (ZT12-ZT14). The light pulse was administered for 5 min beginning at minute 0 (ZT13; hatched vertical bar, panels B,D,F). Dotted data line - Tc obtained with DSI transmitters; solid data line - DSI activity index. N=9-11/group.