Article Figures & Data
Figures
- Figure 1.
Establishing high versus low alcohol intake in male and female rats. a, Time line of experiment: rats underwent 10 weeks of intermittent access to the IA2BC20% and water paradigm, with ketamine self-administration nested from week 4 to 7 and incubation of ketamine-craving tests from week 8 to 10. Rats received bilateral HSV-GFP injections into the NAc after 10 weeks of alcohol intake and were killed 3 d later. b, c, Distribution of alcohol intake (in grams per kilogram) and preference (percentage) for alcohol during the third week of intake. A median split was used to determine cutoffs for high and low alcohol intake: high-alcohol intake male rats (n = 15), low-alcohol intake male rats (n = 16); high-alcohol intake female rats (n = 15), and low-alcohol intake female rats (n = 16). **p < 0.01, ***p < 0.001. Data are represented as mean ± SEM average alcohol intake (a) and preference (b).
- Figure 2.
Ketamine acquisition under the FR1 schedule of reinforcement is reduced in high-alcohol intake male rats, but not female rats. a, b, Number of ketamine or saline infusions under an FR1 schedule of reinforcement during 2 h sessions in male and female rats, respectively. a, Infusions were significantly decreased in high-alcohol intake male rats (n = 8) in session 4 compared with low-alcohol intake rats (n = 8) and session 5 to water-intake rats (n = 11). Female rats self-administered more ketamine than males, and high-alcohol intake female rats were significantly higher than high-alcohol intake male rats for the final two FR1 sessions (SA sessions 10–11). b, No intake differences were observed in saline self-administering rats of either sex. c, d, Number of active and inactive responses during FR1 sessions in male and female rats. Responses include the number of nose pokes rewarded and unrewarded during the 20 s timeout period. c, High-alcohol intake male rats decreased active responses in session 5 compared with water-intake males and session 6 compared with low-alcohol intake males, and an overall reduction was observed during the final two FR1 sessions (SA sessions 10–11). Water-intake females (n = 11) showed a significant increase in active responses compared with males in session 2, while high-alcohol intake females (n = 7) displayed this sex difference from sessions 3 to 6 and low-alcohol (n = 8) from sessions 5 to 6. d, Intake did not affect responding in the saline groups. The *, #, @, &, ^ p < 0.05 symbols represent either within- or between-sex differences (indicated in a and c). Data are represented as the mean ± SEM infusions or responses for ketamine (0.5 mg/kg/infusion) or saline. Saline self-administration male and female rats with water intake (n = 11), low alcohol intake (n = 8), and high alcohol intake (n = 7). Low-alcohol intake female rats that self-administered ketamine (n = 8). **p < 0.01.
- Figure 3.
Motivation to self-administer ketamine is not maintained in either sex, but high-alcohol intake female rats show enhanced motivation during the second session. a, b, PR break-point data in rats that self-administered ketamine and saline. In the ketamine groups, water-intake females (n = 11) have significantly higher break points than males on the first session (SA session 7). High-alcohol intake females (n = 7) have significantly increased break points in SA sessions 8–9, while low-alcohol intake females (n = 8) have increased break points in SA session 9. The male groups that self-administered ketamine have increased break points compared with saline only for the first two sessions (SA sessions 8–9) before they decrease, whereas water-intake females are only significantly higher than saline in SA session 7, low-alcohol only in SA session 9, and high-alcohol in SA sessions 8 and 9. c, d, Number of active responses during the PR sessions for rats that self-administered ketamine or saline. Data from active responses parallel break-point data with the exception that water-intake females that self-administered ketamine did not show differences from the saline groups. e, f, Number of ketamine or saline infusions under a PR schedule of reinforcement. Sessions ended after failure to achieve the next ratio in a 1 h time period. Males and females self-administered significantly more ketamine infusions compared with saline across all three sessions. High-alcohol intake females took significantly higher rates of ketamine compared with low-alcohol or water-intake females. *, #, &, @, ^ p < 0.05 symbols represent either within- or between-sex differences (indicated in e). Data are represented as the mean ± SEM break point and ketamine (0.5 mg/kg/infusion) or saline infusions. Saline self-administration male and female rats with water intake (n = 11), low alcohol intake (n = 8), and high alcohol intake (n = 7). **p < 0.01.
- Figure 4.
Incubation of ketamine craving develops in all groups except low-alcohol intake female rats. a, b, Active responses during 2 h FR1 sessions 1, 7, and 21 d into the ketamine abstinence period in male and female rats. Drug-paired cues were identical, but active responses yielded no drug infusion. Female rats displayed increased levels of active responding compared with males, regardless of ketamine or saline self-administration. a, In male rats, active responses within the ketamine groups (water, n = 11; low-Alc, n = 8; high-Alc, n = 8) increased over the 21 d period. In female rats, those that self-administered ketamine (water, n = 11; low-Alc, n = 7; high-Alc, n = 7) that were considered water- and high-alcohol intake rats increased responding over time; however, low-alcohol intake female rats did not. b, In male rats, intake did not affect active responding in the saline groups (water, n = 11; low-Alc, n = 8; high-Alc, n = 7). Water-intake female rats that self-administered saline increased responding over time while the alcohol groups did not (water, n = 9; low-Alc, n = 8; high-Alc, n = 7). *p < 0.05, **p < 0.01. Data are expressed as the mean ± SEM active responses.
- Figure 5.
Ketamine decreases alcohol intake in high-alcohol intake male rats while increasing it in low-alcohol intake females. a, b, Alcohol intake (g/kg/24 h) over a 10 week period, with self-administration of ketamine or saline occurring from week 4 to 7 (indicated by shaded rectangles). a, In high-alcohol intake male rats, self-administration of ketamine (n = 8) blocks the escalation in alcohol intake observed in saline rats (n = 7). Ketamine had no effect on high-alcohol intake female rats (Sal, n = 7; Ket, n = 8). b, In low-alcohol intake male rats, ketamine had no effect on alcohol intake (Sal, n = 8; Ket, n = 8). In low-alcohol intake female rats, ketamine self-administration enhanced alcohol intake compared with saline from session 19 (week 7) to 28 (week 9; Sal, n = 8; Ket, n = 8). *p < 0.05. Data are expressed as the mean ± SEM alcohol preference. *, #p < 0.05; symbols represent either within- or between-sex differences (indicated on Fig. 5a,b), ****p < 0.0001.
- Figure 6.
Ketamine decreases preference for alcohol in high-alcohol intake male rats while increasing it in low-alcohol intake females. a, b, Alcohol preference (percentage) over a 10 week period, with self-administration of ketamine or saline occurring from week 4 to 7 (indicated by shaded rectangles). a, In male rats, self-administration of ketamine (n = 8) blocks the escalation in alcohol preference observed in high-alcohol intake saline (n = 7) rats. Preference was significantly attenuated from session 18 (week 6) to 31 (week 10). In high-alcohol intake female rats, ketamine had no effect on preference (Sal, n = 7; Ket, n = 8). b, In low-alcohol intake male rats, ketamine had no effect on preference (Sal, n = 8; Ket, n = 8). In low-alcohol intake female rats, preference for alcohol was enhanced in rats that self-administered ketamine compared with saline from session 19 (week 7) to 28 (week 9; Sal, n = 8; Ket, n = 8). *p < 0.05. Data are expressed as the mean ± SEM alcohol preference.*, #p < 0.05; symbols represent either within- or between-sex differences (indicated on Fig. 5a,b), **p < 0.01.
- Figure 7.
Dendritic spine density changes in the NAc are differentially impacted depending on sex and intake. a, Representative image of HSV-GFP expression in the NAc. b, Representative image of dendritic spines after deconvolution and 3D reconstruction featuring examples of thin, mushroom, and stubby spine shapes. DH, Head diameter; DN, neck diameter. c, High alcohol intake increases total spine density in rats of both sexes compared with water-intake control rats. d, High alcohol intake in male rats shows increases in thin spine density, and ketamine reduces thin spines in male rats compared with saline. Ketamine reduces thin spine density in water-intake female rats compared with saline, and both alcohol-intake groups show rescuing of these deficits. e, Water intake and low alcohol intake increase mushroom spines in ketamine self-administration male rats compared with saline self-administration male rats, but this effect was not observed in high-alcohol intake males. Ketamine increased mushroom spines in female rats compared with saline, regardless of intake. f, Stubby spines are unaffected by sex, intake, or treatment. g, Representative images with 3D reconstructed models of dendritic spines for each treatment and intake group. *, #, @, ^ p < 0.05 symbols represent either within- or between-group differences (indicated in c and f; n = 3 and 4/group; for n = 3, 10–12 dendrites/rat; for n = 4, 8–12 dendrites/rat). **p < 0.01, ***p < 0.001.
- Figure 8.
Alcohol preference is correlated with total and thin spines, while ketamine infusions are correlated with mushroom spine changes in rats of both sexes. a, b, Linear regression depicting positive correlations between alcohol preferences during the final week of consumption with total and thin spines, respectively. c, Mushroom spines did not correlate with alcohol preference during the final week of drinking. d, Total spines did not correlate with cumulative infusions during the self-administration period in either sex. e, In male rats, thin spines negatively correlated with cumulative infusions during the self-administration period, but this was not observed in females. f, Linear regression depicting positive correlation between mushroom spines and cumulative infusions during the self-administration sessions. R 2 and p values for each correlation are listed within their respective figure.
Tables
Figure Comparison Type of test Statistic 95% CI a NA Sucrose pellets Four-way LMM ANOVA Sex × intake × treatment × sessions: F(8,364) = 0.85 p = 0.56 b NA Alcohol (g/kg), weeks 1–3 Three-way LMM ANOVA Sex: F(1,59) = 48.42 p < 0.0001 c NA Alcohol (%pref), weeks 1–3 Three-way LMM ANOVA Sex: F(1,58) = 17.61 p < 0.0001 d 1b,c Week 3 average alcohol intake and preference Unpaired t tests Intake: t(60) = 4.66
Preference: t(60) = 2.74p < 0.0001
p = 0.0081b Average alcohol (g/kg) Frequency distribution, median split Cutoff
males: 4.3 g/kg
females: 6.9 g/kgNA 1c Average alcohol (%) Frequency distribution, median split Cutoff
males: 16%,
females: 23%NA e NA Body weight, weeks 1–3 Three-way LMM ANOVA Sex: F(1,93) = 736.83 p < 2e−16 NA Body weight, weeks 1–10 Four-way LMM ANOVA Sex × intake × treatment × sessions: F(60,2790) = 1.57 p = 0.004 NA Males: body weight, weeks 1–10 Three-way LMM ANOVA Intake × treatment × sessions: F(60,1410) = 1.75 p = 0.0004 NA Water intake: Ket SA vs Sal SA Tukey’s post hoc Sessions 17–31: t < −2 Sessions 17-31: p < 0.05 g 2a,b FR1 infusions, sessions 1–6 Four-way LMM ANOVA Sex: F(1,93) = 9.02 p = 0.0034 2a,b FR1 Infusions, sessions 10–11 Four-way LMM ANOVA Sex × intake: F(2,93) = 3.45 p = 0.036 2a,b High-Alc: F vs M Tukey’s post hoc SA sessions 10–11: t(93) = 3.05 p = 0.003 2a,b Males: FR1 Infusions, sessions 1–6 Three-way LMM ANOVA Intake × treatment × sessions: F(10,230) = 2.3 p = 0.014 2a Males_Ket SA: high vs low and high vs water Tukey’s post hoc SA session 4: t(46) = −2.8
SA session 5: t(46) = −3.13Session 4: p = 0.02
Session 5: p =0.008Males: FR1 infusions, sessions 10–11 Three-way LMM ANOVA Intake × treatment: F(2,46) = 3.83 p = 0.029 Ket SA: high-Alc vs water Tukey’s post hoc t(46) = −2.5 p = 0.04 Ket SA: high-Alc vs low_Alc Tukey’s post hoc t(46) = −3.005 p = 0.012 2a,b Females: FR1 Infusions, sessions 1–6 Three-way LMM ANOVA Treatment × sessions: F(5,235) = 38.03 p < 0.0001 Females: FR1 Infusions, sessions 10–11 Three-way LMM ANOVA Treatment × sessions: F(1,47) = 6.11 p = 0.017 h 2c,d Active responses, sessions 1–6 Four-way LMM ANOVA Sex × intake × treatment × sessions: F(10,459) = 2.13 p = 0.021 2c Ket SA_water: F vs M Tukey’s post hoc SA session 2: t(93) = 2.33 p = 0.022 2c Ket SA_low-Alc: F vs M Tukey’s post hoc SA sessions 5–6: t(93) = 2.18, 2.62 p = 0.032, 0.01 2c Ket SA_high-Alc: F vs M Tukey’s post hoc SA sessions 3–6: t(93) = 3.51, 3.53, 4.54, 4.59 p = 0.0007, 0.0007, 0.0001, 0.0001 2c,d Active responses, sessions 10–11 Four-way LMM ANOVA Sex: F(1,93) = 9.93 p = 0.002 2c,d Inactive responses, sessions 1–6 Four-way LMM ANOVA Sex: F(1,94) = 4.1 p = 0.04 Inactive responses, sessions 10–11 Four-way LMM ANOVA Sex × intake × treatment × sessions: F(2,90) = 0.35 p = 0.71 2c,d Males: active responses, sessions 1–6 Three-way LMM ANOVA Intake × treatment × sessions: F(10,228) = 3.13 p = 0.0009 2c Males_Ket SA: high vs water Tukey’s post hoc SA sessions 5–6: t(46) = −3.59, −2.95 p = 0.002, 0.01 2c,d Males: active response, sessions 10–11 Three-way LMM ANOVA Intake × treatment: F(2,46) = 3.65 p = 0.034 2c Males_Ket SA: high vs water Tukey’s post hoc Main effect of intake: t(46) = −3.17 p = 008 2c,d Females: active response, sessions 1–6 Three-way LMM ANOVA Treatment × sessions: F(5,231) = 26.44 p < 0.0001 2c,d Females: active response, sessions 10–11 Three-way LMM ANOVA Intake × treatment × sessions: F(2,46) = 4.12 p = 0.02 2c Ket SA: high-Alc vs water Tukey’s post hoc SA session 10: t(46) = 2.77 p = 022 i 3a,b PR break point Four-way LMM ANOVA Sex × intake × treatment × sessions: F(4,186) = 3.6 p = 0.0074 3a Ket SA_water: F vs M Tukey’s post hoc SA session 7: t(93) = 2.21 p = 0.029 3a Ket SA_low-Alc: F vs M Tukey’s post hoc SA session 9: t(93) = 3.29 p = 0.0014 3a Ket SA_high-Alc: F vs M Tukey’s post hoc SA sessions 8–9: t(93) = 5.27, 3.32 p = 0.0001, 0.0013 3a,b Males: break point Three-way LMM ANOVA Treatment × sessions: F(2,92) = 3.21 p = 0.045 3a,b M_Ket vs Sal Tukey’s post hoc SA sessions 7–8: t(46) = 4.08, 2.94 p = 0.0002, 0.0052 3a,b Females: break point Three-way LMM ANOVA Intake × treatment × sessions: F(4,94) = 3.67 p = 0.008 3a,b F_Water: Ket vs Sal SA Tukey’s post hoc SA session 7: t(47) = 2.25 p = 0.029 3a,b F_Low-Alc: Ket vs Sal SA Tukey’s post hoc SA session 9: t(47) = 2.52 p = 0.015 3a,b F_High-Alc: Ket vs Sal SA Tukey’s post hoc SA session 8: t(47) = 3.67 p = 0.0006 3a F_Ket SA: high vs water and high vs low Tukey’s post hoc SA session 8: t(47) = 3.94, 3.78 p = 0.0008, 0.012 j 3c,d PR active responses Four-way LMM ANOVA Sex × intake × treatment × sessions: F(4,185) = 3.25 p = 0.013 3c Ket SA_water: F vs M Tukey’s post hoc SA session 7: t(93) = 1.99 p = 0.049 3c Ket SA_low-Alc: F vs M Tukey’s post hoc SA session 9: t(93) = 3.27 p = 0.0015 3c Ket SA_high-Alc: F vs M Tukey’s post hoc SA sessions 8–9: t(93) = 5.2, 3.43 p = 0.0001, 0.0009 3c,d Males: PR active responses Three-way LMM ANOVA main effect of treatment: F(1,46) = 10.43 p = 0.0023 3c,d Females: active responses Three-way LMM ANOVA Intake × treatment × sessions: F(4,94) = 3.25 p = 0.015 3c,d F_low-Alc: Ket vs Sal SA Tukey’s post hoc SA session 9: t(47) = 2.48 p = 0.017 3c,d F_high-Alc: Ket vs Sal SA Tukey’s post hoc SA session 8: t(47) = 3.65, 2.05 p = 0.0007, 0.0047 3c F_Ket SA: high vs water and high vs low Tukey’s post hoc SA session 8: t(47) = 3.88, 3.76 p = 0.0009, 0.0014 k 3e,f PR infusions Four-way LMM ANOVA Sex × intake × treatment × sessions: F(4,186) = 2.95 p = 0.022 3e Ket SA_water: F vs M Tukey’s post hoc SA session 7: t(93) = 2.26 p = 0.026 3e Ket SA_low-Alc: F vs M Tukey’s post hoc SA session 9: t(93) = 2.69 p = 0.0084 3e Ket SA_high-Alc: F vs M Tukey’s post hoc SA sessions 8–9: t(93) = 4.04, 3.54 p = 0.0001, 0.0006 3e,f Males: infusions Three-way LMM ANOVA Treatment × sessions: F(2,92) = 4.32 p = 0.016 3e,f M_Ket vs Sal Tukey’s post hoc SA sessions 7–9: t(46) = 5.48, 4.17, 2.09 p = 0.0001, 0.0001, 0.04 3e,f Females: infusions Three-way LMM ANOVA Intake × treatment × sessions: F(4,94) = 4.48 p = 0.002 3e,f F_water: Ket vs Sal SA Tukey’s post hoc SA sessions 7, 9: t(47) = 3.82, 2.03 p = 0.0004, 0.049 3e,f F_low-Alc: Ket vs Sal SA Tukey’s post hoc SA session 9: t(47) = 2.71 p = 0.005 3e,f F_high-Alc: Ket vs Sal SA Tukey’s post hoc SA session 8: t(47) = 2.96 p = 0.009 3e F_Ket SA: high vs water and high vs low Tukey’s post hoc SA session 8: t(47) = 2.9, 3.19 p = 0.02, 0.007 l 4a,b Incubation of craving, active responses Four-way LMM ANOVA Sex: F(1,85) = 9.81 p = 0.0024 4a,b Males: incubation of craving, active responses Three-way LMM ANOVA Treatment × sessions: F(1,85) = 3.79 p = 0.026 4a,b Males: incubation of craving, active responses Three-way LMM ANOVA Intake × treatment: F(2,44) = 5.44 p = 0.008 4a M_water, Ket SA: day 1 vs 21 Tukey’s post hoc t(91) = 2.52 p = 0.03 4a M_low-Alc, Ket SA: day 1 vs 7, 1 vs 21 Tukey’s post hoc t(91) = 3.44, 4.05 p = 0.0025, 0.0003 4a M_high-Alc, Ket SA, day 1 vs 7 Tukey’s post hoc t(91) = 2.72 p = 0.02 4a,b Females: incubation of craving, active responses Three-way LMM ANOVA Intake × treatment: F(2,41) = 3.93 p = 0.027 4b F_water, Sal SA: day 1 vs 7, 1 vs 21 Tukey’s post hoc t(82) = 2.8, 2.8 p = 0.01, 0.01 4a F_water, Ket SA: day 1 vs 21 Tukey’s post hoc t(82) = 2.8 p = 0.01 4a F_high-Alc, Ket SA, day 1 vs 7 Tukey’s post hoc t(82) = 2.52 p = 0.04 m 5a,b Alcohol (g/kg), weeks 1–10 Four-way LMM ANOVA Sex: F(1,53) = 83.87 p < 0.0001 5a,b Males: g/kg weeks 1–10 Three-way LMM ANOVA Intake × treatment × sessions: F(30,785) = 2.53 p < 0.0001 5a High-Alc: Ket SA vs Sal SA Tukey’s post hoc Sessions 19, 22: t(27) < −2.68, −3.08 p = 0.019, 0.009 5a,b Females: g/kg weeks 1–10 Three-way LMM ANOVA Intake × sessions: F(30,760) = 2.5; treatment × sessions: F(30,760) = 1.6 p < 0.0001; p = 0.022 5b Low-Alc: Ket SA vs Sal SA Tukey’s post hoc Sessions 19–20, 23–26: t(27) > 2.26 p < 0.05 n 6a,b Alcohol (%pref), weeks 1–10 Four-way LMM ANOVA Sex: F(1,53) = 6.19 p = 0.016 6a,b Males: %pref weeks 1–10 Three-way LMM ANOVA Intake × treatment × sessions: F(30,784) = 2.28 p = 0.0001 6a High-Alc: Ket SA vs Sal SA Tukey’s post hoc Sessions 19–23, 25–31: t(27) < −2.07 p < 0.05 6a,b Females: %pref weeks 1–10 Three-way LMM ANOVA Intake × treatment × sessions: F(30,759) = 1.67 p = 0.015 6b Low-Alc: Ket SA vs Sal SA Tukey’s post hoc Sessions 19–20, 22–26: t(26) > 2.11 p < 0.05 o 7c Total spines Three-way LMM ANOVA Sex × intake: F(2,26) = 4.77 p = 0.017 7c High-Alc: M vs F Tukey’s post hoc t(26) = −4.17 p = 0.0003 7c Males: total spines Two-way LMM ANOVA Intake: F(2,13) = 3.84 p = 0.04 High-Alc vs water Tukey’s post hoc t(15) = 2.87 p = 0.02 7c Females: total spines Two-way LMM ANOVA Intake: F(2,13) = 16.23 p = 0.00029 p 7d Thin spines Three-way LMM ANOVA Sex: F(1,26) = 9.63 p = 0.005 7d Males: thin spines Two-way LMM ANOVA Treatment: F(2,13) = 30.63 p < 0.0001 7d Females: thin spines Two-way LMM ANOVA Intake × treatment: F(2,13) = 3.92 p = 0.047 7d Sal SA: high-Alc vs water Tukey’s post hoc t(13) = 3.67 p = 0.008 7d Ket SA: low-Alc vs water Tukey’s post hoc t(15) = 5.25 p = 0.0004 7d Ket SA: high-Alc vs water Tukey’s post hoc t(15) = 4.72 p = 0.001 7d Water: Ket SA vs Sal SA Tukey’s post hoc t(15) = −3.47 p = 0.004 q 7e Mushroom spines Three-way LMM ANOVA Sex × intake × treatment: F(2,26) = 8.82 p = 0.001 7e Males vs females: high-Alc, Ket SA Tukey’s post hoc t(26) = −6.22 p < 0.0001 7e Males vs Females: low-Alc, Ket SA Tukey’s post hoc t(26) = 2.6 p = 0.01 7e Males: mushroom spines Two-way LMM ANOVA Intake × treatment: F(2,13) = 12.08 p = 0.001 7e Water: Ket SA vs Sal SA Tukey’s post hoc t(13) = 5.21 p = 0.0005 7e Low-Alc: Ket SA vs Sal SA Tukey’s post hoc t(13) = 7.16 p < 0.0001 7e High-Alc: Ket SA vs Sal SA Tukey’s post hoc t(13) = 0.21 p = 0.83 7e Females: mushroom spines Two-way LMM ANOVA Treatment: F(1,13) = 72.6 p < 0.0001 r 7f Stubby spines Three-way LMM ANOVA Sex × intake × treatment: F(2,26) = 0.02 p = 0.97 s 8a Total × alcohol (%pref) Linear regression Males: R 2 = 0.54
Females: R 2 = 0.49p = 0.007
p = 0.018b Thin × alcohol (%pref) Linear regression Males: R 2 = 0.35
Females: R 2 = 0.35p = 0.04
p = 0.048c Mushroom × alcohol (%pref) Linear regression Males: R 2 = 0.06
Females: R 2 = 0.1p = 0.44
p = 0.31t 8d Total × Cum. infusions Linear regression Males: R 2 = 0.17
Females: R 2 = 0.09p = 0.08
p = 0.218e Thin × Cum. infusions Linear regression Males: R 2 = 0.3
Females: R 2 = 0.007p = 0.01
p = 0.738f Mushroom × Cum. infusions Linear regression Males: R 2 = 0.18
Females: R 2 = 0.56p = 0.07
p = 0.003Summary of analyses performed on behavioral, morphologic, and correlational data. Each comparison is indicated by lettering in the far-left column (column 1). Figure column represents each corresponding to that figure or panel for that comparison. Comparison column represents the dependent variable being measured as well as individual comparisons examined with post hoc tests. Type of test indicates the analysis performed on that particular dataset. Statistic column indicates sample size, df, and F statistic for each comparison. Statistical interactions and/or main effects observed are indicated within this column. Confidence interval (CI) set at 95% lists the corresponding p values for each statistic, and any comparison p < 0.05 was considered statistically significant. NA, Not applicable; Cum., cumulative; LMM ANOVA, linear mixed-models ANOVA. %pref, percentage of preference; F, female; M, male.
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