Article Figures & Data
Figures
- Figure 1.
A, Experimental timeline of cocaine CPP study 1. B, Following conditioning to 8 mg/kg cocaine, most animals undisturbed before cocaine conditioning trials spent more time in the cocaine-paired side following conditioning as expected as compared with their preconditioning test times (top), which shifted to all animals when SD occurred immediately before cocaine conditioning trials (bottom). C, SD immediately before cocaine conditioning trials induced preference to 3 mg/kg cocaine and enhanced preference to 8 mg/kg cocaine without altering preference to 15 mg/kg cocaine. SD in the absence of cocaine (0 mg/kg) did not induce preference. Asterisks above columns indicate preference (as determined by a significant difference from 0), the carrot between columns indicates a significant difference between groups, and n.s. indicates a lack of significant difference between groups. Bars indicate group average, error bars indicate standard error of the mean (SEM).
- Figure 2.
A, Experimental timeline for the cocaine CPP study 2. B, Following conditioning to 8 mg/kg cocaine, most animals undisturbed before the postconditioning test spent more time in the cocaine-paired side as compared with their preconditioning test times (top), which shifted to a higher proportion of animals when SD occurred immediately before the postconditioning test (bottom). C, SD immediately before postconditioning test induced a non-significant trend toward preference to 3 mg/kg cocaine and enhanced preference to 8 mg/kg cocaine, while reducing preference to a non-significant trend to 15 mg/kg cocaine. Asterisks above columns indicate preference (as determined by a significant difference from 0), the carrot between columns indicates a significant difference between groups, and n.s. indicates a lack of significant difference between groups. Bars indicate group average, error bars indicate SEM.
- Figure 3.
A, Experimental timeline for the cocaine CPP study 3. B, All animals spent more time in the cocaine-paired side following conditioning as compared with their preconditioning test values when Veh was administered before the cocaine trials (top) or when SB 334867 was administered immediately following SD (bottom); however, only a subset of animals spent more time in the cocaine-paired side when SB 334867 was administered in the absence of SD (right side). C, OX1R antagonism before cocaine conditioning trials blocked the SD-induced preference to 3 mg/kg cocaine and the SD-induced enhanced preference to 8 mg/kg cocaine, while OX1R antagonism in the absence of SD prevented the acquisition of preference to 8 mg/kg cocaine. Asterisks above columns indicate preference (as determined by a significant difference from 0), and n.s. indicates a lack of significant difference between groups. Bars indicate group average, error bars indicate SEM.
- Figure 4.
A, Experimental timeline for cocaine CPP study 4. B, Most animals spent more time in the cocaine-paired side following conditioning as compared with their preconditioning test values both when undisturbed animals were administered SB 334687 before the postconditioning test (top) and when sleep-deprived animals were administered SB 334867 before the postconditioning test (bottom). C, OX1R antagonism prevents the SD-induced increase in preference to 8 mg/kg cocaine, although both groups show preference for the cocaine-paired side. Asterisks above columns indicate preference (as determined by a significant difference from 0), and n.s. indicates a lack of significant difference between groups. Bars indicate group average, error bars indicate SEM.
- Figure 5.
A, Dose-response plot of preference from cocaine CPP study 1 in which SD shifts the curve leftward (data replotted from Fig. 1C). B, OX1R antagonism mitigates the SD-induced shift in the dose-response curve (data replotted from Figs. 1C, 3C). C, Dose-response plot of preference from cocaine CPP study 2 in which SD shifts the curve leftward, although to a lesser degree than under cocaine CPP study 1 (data replotted from Fig. 2C). D, The SD enhancement of relative preference, as determined by the ratio of average preference in SD and noSD groups (from study 2) and indicated by >1 value (left bar), is blocked by OX1R antagonism (SD SB/noSD SB from study 4; right bar). Notably, the relative preference of <1 under OX1R antagonism indicates that OX1R antagonism in the presence of SD reduces relative preference, while OX1R antagonism in the absence of SD increases relative preference.
Tables
0 mg/kg 3 mg/kg Study 1 noSD Sal, no SD. Sal SD. Sal, noSD Sal noSD Coc, SD. Sal SD. Coc, noSD Sal N 12 12 10 11 Mean ± SEM 97.81 ± 52.49 100.6 ± 63.38 41.83 ± 90.53 180.4 ± 62.75 95% CI −17.73−213.4 −49.92−251.1 −163−246.6 40.56−320.2 p value 0.09 0.17 0.655 0.0165 Stat used for comparison One sample t test One sample t test One sample t test One sample t test 8 mg/kg 15 mg/kg noSD Coc, SD. Sal SD. Coc, noSD Sal noSD Coc, SD. Sal SD. Coc, noSD Sal N 12 12 12 12 Mean ± SEM 126.4 ± 83.62 348.7 ± 62.95 257.9 ± 65.4 284.9 ± 94.67 95% CI −57.64−310.5 210.1−487.2 114−401.9 76.5−493.2 p value 0.1588 0.0002 0.0023 0.0119 Stat used for comparison One sample t test One sample t test One sample t test One sample t test Group comparison 0 mg/kg 3 mg/kg 8 mg/kg 15 mg/kg Difference between means −2.521 ± 49.26 −138.5 ± 108.5 −222.3 ± 104.7 −26.93 ± 115.1 95% CI −104.7−99.63 −365.6−88.46 −439.3 to −5.173 −265.6−211.7 p value 0.9596 0.11 0.0226 0.4085 Stat used for comparison Unpaired t test, two tailed Unpaired t test, one tailed Unpaired t test, one tailed Unpaired t test, one tailed 3 mg/kg 8 mg/kg 15 mg/kg Study 2 noSD SD noSD SD noSD SD N 12 11 13 11 12 12 Mean ± SEM 128.3 ± 76.91 187.4 ± 94.94 141.3 ± 49.55 256 ± 42.39 281.8 ± 72.06 179.6 ± 100.1 95% CI −41.02−297.5 −24.19−398.9 33.35−249.3 161.6−350.5 123.2−440.4 −40.84−400 p value 0.1236 0.0767 0.0146 0.0001 0.0024 0.1005 Stat used for comparison One sample t test One sample t test One sample t test One sample t test One sample t test One sample t test Group comparison 3 mg/kg 8 mg/kg 15 mg/kg Difference between means −59.11 ± 121.3 114.7 ± 66.55 102.3 ± 123.4 95% CI −311.3−193.1 −23.31−252.7 −153.6−358.1 p value 0.3155 0.0494 0.2081 Stat used for comparison Unpaired t test, one tailed Unpaired t test, one tailed Unpaired t test, one tailed 3 mg/kg 8 mg/kg Study 3 noSD Veh Coc, SD SB Sal SD SB Coc, noSD Veh Sal noSD Veh Coc, SD SB Sal SD SB Coc, noSD Veh Sal noSD SB Coc, noSD Veh Sal N 11 12 11 11 11 Mean ± SEM 48.12 ± 48.24 70.25 ± 93.15 282 ± 68.44 246.8 ± 37.69 141.8 ± 102.1 95% CI −59.36−155.6 −134.8−275.3 129.5−434.5 162.8−330.7 −85.82−369.4 p value 0.342 0.4666 0.0021 <0.0001 0.1953 Stat used for comparison One sample t test One sample t test One sample t test One sample t test One sample t test Group comparison 3 mg/kg
noSD Veh Coc, SD SB Sal vs SD SB Coc, noSD Veh Sal8 mg/kg noSD Veh Coc, SD SB Sal vs SD SB Coc, noSD Veh Sal 8 mg/kg noSD Veh Coc, SD SB Sal vs noSD SB Coc, noSD Veh Sal Difference between means 22.13 ± 107.8 35.25 ± 105 140.2 ± 105 95% CI −202.1−246.4 −211.9−282.4 −106.9−387.4 p value 0.8394 0.9321 0.3467 Stat used for comparison Unpaired t test, two tailed One-way ANOVA with Sidak correction for multiple comparisons One-way ANOVA with Sidak correction for multiple comparisons Study 4 8 mg/kg noSD SB SD SB N 12 12 Mean ± SEM 237.4 ± 57.03 152.2 ± 50.88 95% CI 111.8−362.9 40.17−264.1 p value 0.0016 0.0123 Stat used for comparison One sample t test One sample t test Group comparison 8 mg/kg Difference between means −85.21 ± 76.42 95% CI −243.7−73.28 p value 0.2769 Stat used for comparison Unpaired t test, two tailed
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