PMC

Genotype differences in O₂C. Abbreviations are the same as in legend to . A: O₂C was measured for 60-min periods in WT (F, n = 7; M, n = 6), A₁RKO (F, n = 7; M, n = 9), A₁-A_2ARKO (F, n = 6; M, n = 7), and A_2ARKO mice (F, n = 7; M, n = 4) mice. The dark period is from 7 PM to 7 AM. B summarizes the top panel. The black column shows the O₂C average between 9 PM and 5 AM; the spotted column for Peak shows the O₂C average between 7:30 PM and 8:30 PM. Data are presented as mean values or mean values ± SE (*P < 0.05 compared with WT mice). C: O₂C (Oxygen) was measured for 16-h mice.

A₁R and A_2AR affect locomotor activity (LA) in sex-dependent manner. Graphs constructed essentially as described in legend to . A and B: LA is recorded for consecutive 30-min periods in mice. The dark period is from 7 PM to 7 AM. C and D: summarizes the corresponding top panels. Mean values or mean values ± SE (*P < 0.05 compared with WT mice; #P < 0.05 compared with A₁RKO mice; **P < 0.05 compared with A_2ARKO mice; ##P < 0.05 compared with A₁-A_2ARKO mice at the corresponding time period) are given. E: LA were measured telemetrically during 24 h and recorded for every consecutive 30-min periods. The data are shown as a 5-day average and presented as mean values or mean values ± SE (*P < 0.05 compared with corresponding female mice). F: normal saline (NS), caffeine/enprofylline (Enp) 7.5 mg/kg or 30 mg/kg, was administered intraperitoneally at 2-h intervals in WT1 (F, n = 5; M, n = 6), WT2 (F, n = 8; M, n = 8), A₁RKO (F, n = 8; M, n = 8), A₁-A_2ARKO (F, n = 8; M, n = 9), and A_2ARKO mice (F, n = 8; M, n = 10). LA is shown as the average from 60 to 90 min after the injection. Data are presented as means ± SE (*P < 0.05 compared with saline injection).

A₁R and A_2AR affect body temperature (Temp) in sex-dependent manner. A and B: abbreviations and mice number are the same as in legend to . Temp is recorded for consecutive 10-min periods in mice. The dark period is from 7 PM to 7 AM. C and D: summarizes the corresponding top panels and periods are as described in . The data are shown as a 5-day average and presented as mean values or mean values ± SE (*P < 0.05 compared with WT mice; #P < 0.05 compared with A₁RKO mice; **P < 0.05 compared with A_2ARKO mice; ##P < 0.05 compared with A₁-A_2ARKO mice at the corresponding time period). E: Temp was measured telemetrically during 24 h and recorded for every consecutive 30-min period. The data are shown as a 5-day average and presented as mean values or mean values ± SE (*P < 0.05 compared with corresponding female mice). F: injection of saline (NS), caffeine/enprofylline (Enp) 7.5 mg/kg or 30 mg/kg, was administered intraperitoneally at 2-h intervals in WT1 (F, n = 5; M, n = 6), WT2 (F, n = 8; M, n = 8), A₁RKO (F, n = 8; M, n = 8), A₁-A_2ARKO (F, n = 8; M, n = 9), and A_2ARKO mice (F, n = 8; M, n = 10). Temp is shown as the average from 70 to 80 min after the injection. Data are presented as means ± SE (*P < 0.05 compared with saline injection).

A₁ and A_2A adenosine receptors (A₁R or A_2AR, respectively) affect heart rate (HR) in sex-dependent manner. A and B: HR is recorded for consecutive 10-min periods in wild-type [WT; Female (F), n = 8; Male (M), n = 8], A₁R-knockout (A₁RKO; F, n = 8; M, n = 8), A_2ARKO (F, n = 8; M, n = 10), and A₁-A_2ARKO (F, n = 8; M, n = 9) mice. The dark period is from 7 PM to 7 AM. C and D: summarizing the corresponding top panels. The value for Day shows the HR average between 9 AM and 5 PM; the value for Night shows the HR average between 9 PM and 5 AM; the value for Peak shows the HR average between 7:30 PM and 7:40 PM. In A–D, data are shown as a 5-day average; data are presented as mean values or mean values ± SE (*P < 0.05 compared with WT mice; #P < 0.05 compared with A₁RKO mice; **P < 0.05 compared with A_2ARKO mice; ##P < 0.05 compared with A₁-A_2ARKO mice at the corresponding time period). E: HR was measured telemetrically during 24 h. The data are shown as a 5-day average and presented as mean values or mean values ± SE (*P < 0.05 compared with corresponding female mice). F: effects of saline and timolol (1 mg/kg) on HR in male mice. The HR was measured at 10-min intervals until 80 min after injection. Data are presented as means ± SE (*compared with WT, P < 0.05; #compared with saline injection, P < 0.05). Abbreviations and mice number are the same as above. G shows the protocol of experiments. bpm, Beats/min; NS, saline.

Effects of chronic caffeine intake on LA and oxygen consumption (O₂C) in mice. After the baseline recording (Water), mice drank tap water with 0.3 g/l caffeine for 7 days (Caffeine). The LAs in the water group are shown as 5-day averages in 30-min intervals, whereas LA data in caffeine group are shown as 3-day averages (days 5, 6, and 7 during chronic caffeine treatment). O₂C is shown as 1-h average. The values are presented as means ± SE (*Compared with Water, P < 0.05). Abbreviations are the same as in legend or otherwise indicated. A and B: chronic caffeine ingestion increased oxygen consumption in WT mice (Water: F, n = 8; M, n = 8; Caffeine: F, n = 7, M, n = 8). It also increased LA in male WT mice but not in female WT mice (Water: F, n = 7; M, n = 6; Caffeine: F, n = 9, M, n = 6). C and D: in A₁RKO mice, chronic caffeine ingestion increased LA in both females and males (Water: F, n = 8; M, n = 8; Caffeine: F, n = 8, M, n = 8) but had no effect on O₂C (Water: F, n = 7; M, n = 9; Caffeine: F, n = 9, M, n = 8). E and F: in A₁-A_2ARKO mice, chronic caffeine ingestion increased LA in males but not in females (Water: F, n = 8; M, n = 10; Caffeine: F, n = 8, M, n = 9). Chronic caffeine ingestion did not affect O₂C (Water: F, n = 6; M, n = 7; Caffeine: F, n = 6, M, n = 7). G and H: in A_2ARKO mice, chronic caffeine ingestion increased O₂C in males but not in females (Water: F, n = 7; M, n = 6; Caffeine: F, n = 7, M, n = 4). LA was not affected in females or males (Water: F, n = 8; M, n = 10; Caffeine: F, n = 8, M, n = 8).