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Research ArticleResearch Article: New Research, Cognition and Behavior

Sleep Deprivation Enhances Cocaine Conditioned Place Preference in an Orexin Receptor-Modulated Manner

Theresa E. Bjorness and Robert W. Greene
eNeuro 2 November 2020, 7 (6) ENEURO.0283-20.2020; https://doi.org/10.1523/ENEURO.0283-20.2020
Theresa E. Bjorness
1Research Service, VA North Texas Health Care System, Dallas, TX 75126-7167
2Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111
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Robert W. Greene
2Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111
3Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111
4International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba 305-8577, Japan
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  • Figure 1.
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    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.
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    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.

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    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.

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    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.

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    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

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    Table 1

    Cocaine CPP, study 1

    0 mg/kg3 mg/kg
    Study 1noSD Sal, no SD. SalSD. Sal, noSD SalnoSD Coc, SD. SalSD. Coc, noSD Sal
    N12121011
    Mean ± SEM97.81 ± 52.49100.6 ± 63.3841.83 ± 90.53180.4 ± 62.75
    95% CI−17.73−213.4−49.92−251.1−163−246.640.56−320.2
    p value0.090.170.6550.0165
    Stat used for comparisonOne sample t testOne sample t testOne sample t testOne sample t test
    8 mg/kg15 mg/kg
    noSD Coc, SD. SalSD. Coc, noSD SalnoSD Coc, SD. SalSD. Coc, noSD Sal
    N12121212
    Mean ± SEM126.4 ± 83.62348.7 ± 62.95257.9 ± 65.4284.9 ± 94.67
    95% CI−57.64−310.5210.1−487.2114−401.976.5−493.2
    p value0.15880.00020.00230.0119
    Stat used for comparisonOne sample t testOne sample t testOne sample t testOne sample t test
    Group comparison0 mg/kg3 mg/kg8 mg/kg15 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 value0.95960.110.02260.4085
    Stat used for comparisonUnpaired t test, two tailedUnpaired t test, one tailedUnpaired t test, one tailedUnpaired t test, one tailed
    • View popup
    Table 2

    Cocaine CPP, study 2

    3 mg/kg8 mg/kg15 mg/kg
    Study 2noSDSDnoSDSDnoSDSD
    N121113111212
    Mean ± SEM128.3 ± 76.91187.4 ± 94.94141.3 ± 49.55256 ± 42.39281.8 ± 72.06179.6 ± 100.1
    95% CI−41.02−297.5−24.19−398.933.35−249.3161.6−350.5123.2−440.4−40.84−400
    p value0.12360.07670.01460.00010.00240.1005
    Stat used for comparisonOne sample t testOne sample t testOne sample t testOne sample t testOne sample t testOne sample t test
    Group comparison3 mg/kg8 mg/kg15 mg/kg
    Difference between means−59.11 ± 121.3114.7 ± 66.55102.3 ± 123.4
    95% CI−311.3−193.1−23.31−252.7−153.6−358.1
    p value0.31550.04940.2081
    Stat used for comparisonUnpaired t test, one tailedUnpaired t test, one tailedUnpaired t test, one tailed
    • View popup
    Table 3

    Cocaine CPP, study 3

    3 mg/kg8 mg/kg
    Study 3noSD Veh Coc, SD SB SalSD SB Coc, noSD Veh SalnoSD Veh Coc, SD SB SalSD SB Coc, noSD Veh SalnoSD SB Coc, noSD Veh Sal
    N1112111111
    Mean ± SEM48.12 ± 48.2470.25 ± 93.15282 ± 68.44246.8 ± 37.69141.8 ± 102.1
    95% CI−59.36−155.6−134.8−275.3129.5−434.5162.8−330.7−85.82−369.4
    p value0.3420.46660.0021<0.00010.1953
    Stat used for comparisonOne sample t testOne sample t testOne sample t testOne sample t testOne sample t test
    Group comparison3 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 SD SB Coc, noSD Veh Sal8 mg/kg noSD Veh Coc, SD SB Sal vs noSD SB Coc, noSD Veh Sal
    Difference between means22.13 ± 107.835.25 ± 105140.2 ± 105
    95% CI−202.1−246.4−211.9−282.4−106.9−387.4
    p value0.83940.93210.3467
    Stat used for comparisonUnpaired t test, two tailedOne-way ANOVA with Sidak correction for multiple comparisonsOne-way ANOVA with Sidak correction for multiple comparisons
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    Table 4

    Cocaine CPP, study 4

    Study 48 mg/kg
    noSD SBSD SB
    N1212
    Mean ± SEM237.4 ± 57.03152.2 ± 50.88
    95% CI111.8−362.940.17−264.1
    p value0.00160.0123
    Stat used for comparisonOne sample t testOne sample t test
    Group comparison8 mg/kg
    Difference between means−85.21 ± 76.42
    95% CI−243.7−73.28
    p value0.2769
    Stat used for comparisonUnpaired t test, two tailed
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Sleep Deprivation Enhances Cocaine Conditioned Place Preference in an Orexin Receptor-Modulated Manner
Theresa E. Bjorness, Robert W. Greene
eNeuro 2 November 2020, 7 (6) ENEURO.0283-20.2020; DOI: 10.1523/ENEURO.0283-20.2020

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Sleep Deprivation Enhances Cocaine Conditioned Place Preference in an Orexin Receptor-Modulated Manner
Theresa E. Bjorness, Robert W. Greene
eNeuro 2 November 2020, 7 (6) ENEURO.0283-20.2020; DOI: 10.1523/ENEURO.0283-20.2020
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