Abstract
Background
Clinical and preclinical alcohol use disorder (AUD) research demonstrates that males and females differ in motivations behind drinking, patterns of drinking behaviors, and alcohol‐related physiological responses and health consequences. Nonhuman primate (NHP) models of AUD have the potential to enhance our understanding of such sex differences. In NHP models, schedule‐induced polydipsia is a common method to initiate ethanol drinking. In males, characteristics of drinking during the final stage of induction, when monkeys consume 1.5 g/kg/day, predict subsequent drinking patterns when monkeys have unlimited access to ethanol. The present study assessed sex differences in those predictive behaviors during induction and characterized patterns and intakes during 6 months of ethanol drinking.
Methods
Eleven singly housed adult cynomolgus monkeys (six male, five female) were induced to consume water, then increasing doses of ethanol for 4 weeks per dose (0.5, 1.0, and 1.5 g/kg) using a 300‐s fixed‐time schedule of food pellet delivery. Following induction, monkeys switched to an “open‐access” regimen wherein water and ethanol were available 22 h/day, 5 days/week.
Results
Predictive relationships between drinking characteristics during the final phase of induction and subsequent open‐access drinking were replicated, with no evidence of sex differences. Although weekly and total ethanol intakes were higher in males over 6 months of open access, the difference did not reach statistical significance. However, there were sex differences in the distribution of ethanol intake across the day. Males drank significantly more when meals were available, whereas females spread their drinking throughout the first half of the session; these differences were exacerbated in Month 2 and remained for the duration of the study.
Conclusions
These results replicate previous findings of a predictive relationship between drinking variables during induction and later open‐access drinking and reveal sex differences in daily patterns of ethanol intake that may inform treatment approaches.
Keywords: alcohol, nonhuman primates, schedule‐induced polydipsia, sex differences
These studies in male and female cynomolgus monkeys replicate previous findings of a predictive relationship between characteristics of drinking during schedule induction and later open‐access drinking. Sex differences in daily patterns of ethanol intake were identified that may inform treatment approaches.

INTRODUCTION
Problematic alcohol drinking is prevalent throughout the United States; nearly 22% of adults report past‐month binge drinking and 6% partake in heavy drinking (National Institute on Alcohol Abuse and Alcoholism [NIAAA], 2025). Additionally, nearly 11% of adults meet the criteria for alcohol use disorder (AUD; NIAAA, 2024), which causes significant health issues and costs the US hundreds of billions of dollars each year (Sacks et al., 2015). Women currently account for ~40% of the AUD population, but the male–female gap in alcohol use is closing. For example, a 2016 meta‐analysis determined that males born in the early 1900s were 2.2 times more likely to consume alcohol, three times more likely to drink problematically and 3.6 times more likely to experience alcohol‐related harm compared with females, whereas males born in the later 1900s were only 1.1, 1.2, and 1.3 times more likely, respectively, than females (Slade et al., 2016). Although preclinical AUD research began to focus on sex differences relatively recently, male‐female differences have been identified across the spectrum of alcohol drinking, including motivations to drinking, patterns of drinking behaviors and physiological responses to alcohol (Flores‐Bonilla & Richardson, 2020). Both clinical and preclinical studies have shown evidence of a faster onset of AUD‐related behaviors and the progression of AUD‐related health consequences in females (e.g., Fama et al., 2020; Towers et al., 2023).
Whereas a great deal of information has been generated in rodent models regarding the neurobiological effects of alcohol, the ability to generate clinically relevant phenotypes that model long‐term drinking is limited in rats and mice. Nonhuman primates (NHPs) provide the most translationally relevant model of chronic ethanol consumption because of their similarity to humans in brain structure and function and other biological characteristics (Phillips et al., 2014; Weerts et al., 2007). Moreover, NHP models lack some obstacles inherent in human‐subjects research, such as psychiatric comorbidities, retrospective characterizations of drinking and the need for cross‐sectional studies. In the model used in the present study, monkeys are trained to drink unadulterated ethanol (4% w/v in water) using a limited‐access schedule induction procedure that optimizes the association between consumption and ethanol's pharmacological effects (Galbo et al., 2022; Vivian et al., 2001). Under this procedure, water is made available while food pellets are delivered under a 300‐s fixed‐time schedule. After 1 month, the ethanol solution is made available. The maximum daily dose of ethanol is increased in a stepwise fashion over 3 months (0.5, 1.0, and 1.5 g/kg per day for 1 month each) before transitioning to 22‐h sessions in which ethanol and water are freely available, termed “open access.” This procedure induces voluntary ethanol drinking that develops into stable, individualized drinking histories and patterns similar to those observed in humans.
Using this paradigm in adult male cynomolgus monkeys, Grant et al. (2008) applied principal component analysis (PCA), principal component regression (PCR), and functional principal component analysis (FPCA) to analyze behavioral data collected during the last stage of induction (1.5 g/kg) and identified five dependent variables that best predicted future drinking phenotypes: (1) number of ethanol “bouts” (defined as a period of consumption without a 5‐min lapse in drinking), (2) volume of the largest ethanol bout, (3) percent of the ethanol dose consumed in the largest bout, (4) number of pellets delivered in State 1, and (5) daily water intake. Additionally, monkeys were classified as “gulpers” or “sippers” based on how quickly 1.5 g/kg ethanol was consumed in a single bout or in multiple bouts, suggesting that these rates also predict long‐term drinking behaviors. This model was also used to determine more granular classifications of drinking in a multi‐cohort study of rhesus monkeys (Baker et al., 2017). Female subjects were included in that study; however, low variability in ethanol consumption in the female NHPs limited conclusions regarding sex differences. Our laboratory has utilized this model to study the effects of rank in the NHP social hierarchy on ethanol drinking. Although there were no differences between dominant‐ and subordinate‐ranked monkeys during induction, subordinate monkeys drank significantly more during 1 year of open‐access drinking (Galbo et al., 2022; Galbo‐Thomma et al., 2023).
The present study investigated whether sex differences exist in the ability of the behavioral phenotypes determined by Grant et al. (2008) to predict ethanol consumption during 6 months of open‐access drinking in cynomolgus monkeys. The primary variables assessed were the number of ethanol bouts, the percent of the 1.5 g/kg ethanol dose consumed in the largest bout, and the number of pellets delivered in State 1. In addition, the time it took monkeys to finish the 1.5 g/kg dose was assessed. Volume‐based measures identified by Grant et al. (2008) were excluded because males and females had different fluid volume requirements as the result of sex‐based weight differences. After completion of induction, amounts and daily patterns of open‐access ethanol drinking over 6 months were characterized and compared.
MATERIALS AND METHODS
Subjects
Eleven adult cynomolgus monkeys (Macaca fascicularis; six males, five females; 7.1 ± 2.0 years of age at the start of the study) served as subjects. Monkeys were singly housed in stainless steel cages (172.5 cm high × 171.5 cm wide × 69.9 cm deep; Allentown Caging; Allentown, New Jersey, United States) that were separated into quadrants with solid partitions (each measuring 81.2 cm high × 80.6 cm wide × 69.9 cm deep) in which water was available ad libitum. Monkeys had visual, auditory, and olfactory access to others in the room, were weighed every other week, and were fed enough food (Grain‐Based Dustless Precision Pellets, BioServe; Flemington, New Jersey), fresh fruit, and vegetables daily to maintain healthy body weights and body scores without becoming obese, as determined by daily inspection and periodic veterinary examinations. Animal housing, handling, and experimental procedures were performed in accordance with the 2011 edition of the National Research Council's Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of Wake Forest University. Environmental enrichment was provided as outlined in the Institutional Animal Care and Use Committee's Non‐Human Primate Environmental Enrichment Plan.
Drinking apparatus
Monkeys were trained to use an operant drinking panel affixed to one quadrant of the cage for ethanol, water and food self‐administration as described previously (Galbo et al., 2022). Briefly, each panel included three lights (red, white, and green) above each of two drinking spouts, a photo‐optic switch below one spout, a response on which resulted in delivery of a 1‐g food pellet and an opening in the center of the panel containing a dowel that could be pulled to activate the drinking spouts and photo‐optic switch. Each drinking spout was connected to a 2‐ or 4‐L bottle containing ethanol (4% w/v) or water, respectively, each of which sat atop a balance that continuously monitored the bottle's weight, which was converted to volume. White lights indicated the start of the session and that the panel was active; green lights illuminated when the dowel was pulled and during fluid flow, and red lights illuminated when food pellets were available. The permanent water supply in each cage was disconnected while sessions were active.
Ethanol self‐administration
Using this operant panel, monkeys underwent a well‐established procedure of schedule induction to induce oral ethanol self‐administration (Galbo et al., 2022; Vivian et al., 2001). In summary, induction consisted of three experimental states in each 16‐h session and was conducted 5 days/week. State 1 was marked by a 300‐s fixed‐time schedule of food delivery. For the first month, only water was available to drink. Following water induction, monkeys were induced to drink increasing amounts of ethanol (0.5, 1.0, and 1.5 g/kg) for 4 weeks each. State 1 ended upon delivery of all pellets or after the monkey consumed the required amount of ethanol for each phase of induction (water induction was equal in volume to 1.5 g/kg induction). During State 2, if the required fluid level was met, only water was available on the opposite spout and pellet delivery was stopped. However, if a monkey did not consume their required fluids prior to delivery of all pellets, only ethanol was available during this state. Once State 3 began, monkeys responded under a one‐response fixed‐ratio schedule of reinforcement (FR 1) using the photo‐optic switch for any food remaining from State 1. For any monkey not finished with their required fluid amount, that spout remained active until the session ended or they finished the required volume. Once the required fluid amount was consumed, only the water spout was active.
Following induction, monkeys had access to the 4% ethanol solution and water 22 h/day, 5 days/week (“open access”). Sessions began at 10:00 a.m. on weekdays with illumination of cue lights above the ethanol and water spouts and ended at 8:00 a.m. the following day. Throughout the session, ethanol and water were freely available when the dowel was pulled. Monkeys also self‐administered food pellets under an FR 1 schedule of reinforcement. The daily food pellet allotment (based on the monkey's weight) was divided into three “meals,” which began 0, 120, and 240 min after the start of the session. Each meal lasted until one‐third of the daily ration had been delivered or until the next meal period began (2 h maximum). The average (±SD) number of drinking sessions over 6 months of open access was 117.1 ± 1.2.
Data analysis
To determine whether there were sex differences in the drinking variables measured during induction, unpaired, two‐tailed t‐tests were performed for each variable. Shapiro–Wilk and Kolmogorov–Smirnov tests were performed to check normality and F‐tests were conducted to check homogeneity of variance; all tests passed. After grouping data from both sexes, simple linear regressions were performed on each variable to determine how each was related to subsequent open‐access ethanol intake. Weekly ethanol intakes (g/kg) during the 6‐month 22‐h open‐access period were analyzed using a two‐way repeated‐measures ANOVA with sex and week as factors, followed by post‐hoc Sidak multiple comparisons tests to determine whether there were differences in mean daily ethanol intakes each week. Daily hourly drinking splits were organized into four bins based on the timing of daily activities: (1) during food availability (hours 1–5, 10 a.m.–3 p.m.), (2) post‐meal afternoon drinking (hours 6–10, 3 p.m.–7 p.m.), (3) overnight drinking (hours 11–19, 7 p.m.–5 a.m.) and (4) morning drinking before the session end (hours 20–22, 5 a.m.–8 a.m.). Note that Bin 2 includes the first hour lights were off and Bin 4 includes the last hour lights were off because monkeys tend to remain active or resume activity, respectively, during these hours (present data; Goonawardena et al., 2018). Ethanol intake during these bins were compared between sexes and over time using a two‐way repeated‐measures ANOVA for each bin using sex and month as factors, followed by post‐hoc Sidak multiple comparisons tests. Where differences were observed, Cohen's d was calculated to determine effect size. All statistical analyses were performed using GraphPad Prism 10.4.2. G*Power software (Version 3.1.9.6) was used to determine that the design could detect an effect size of 0.21. In all cases, significance was accepted when p < 0.05.
RESULTS
Drinking characteristics during induction
Unpaired, two‐tailed t‐tests revealed no significant differences between males and females in the number of pellets delivered in State 1 (Figure 1A), the percent of dose consumed in the largest bout (Figure 1B), the time to finish the 1.5 g/kg dose (Figure 1C), or the number of bouts (Figure 1D). Because no sex differences were observed, data from all monkeys were combined for subsequent analyses. Simple linear regressions relating each variable to open‐access ethanol intake were performed (Figure 2). A significant negative relationship was observed between the number of pellets earned in State 1 and ethanol intake (r 2 = 0.420, F(1, 9) = 6.569, p = 0.030; Figure 2A). The percent of dose consumed in the largest bout was positively related to ethanol intake (r 2 = 0.418, F(1, 9)= 6.457, p = 0.032; Figure 2B). Lower ethanol intake was associated with a longer time to finish (r 2 = 0.357, F(1, 9)= 5.003, p = 0.052; Figure 2C) and a higher number of bouts (r 2 = 0.263, F(1, 9)= 3.208, p = 0.107; Figure 2D), but these relationships did not reach statistical significance.
FIGURE 1.

Drinking variables during induction [(A), pellets delivered in State 1; (B) percent of dose consumed during the largest bout; (C) time to finish 1.5 g/kg dose; (D) number of bouts] in males (filled symbols) and females (open symbols). Points represent data from individual subjects (see legend), with the horizontal line indicating the mean.
FIGURE 2.

Regression plots of induction drinking variables vs. open‐access ethanol intake in males (filled symbols as in Figure 1) and females (open symbols as in Figure 1). The solid line across each graph represents the line of best fit. Dashed lines indicate 95% confidence intervals.
Ethanol drinking during 6 months of open access
Although male monkeys drank more ethanol compared with females on most weeks, no statistically significant difference in ethanol intake was found over the 6 months of open access (Figure 3, top). A two‐way ANOVA indicated no main effects of week or sex, and post hoc multiple comparisons revealed no single week in which the sexes differed in ethanol intake. Similarly, no significant sex difference was found in cumulative ethanol intakes over 6 months of drinking (Figure 3, bottom). The average proportion of the total daily ethanol intake consumed in each hour during the first and second months of open‐access drinking is shown in Figure 4A,B, respectively. Figure 4 also delineates the four pre‐defined bins of drinking used for the analysis presented in Figure 5. For both males and females, most of the ethanol was consumed during meals (Bin 1). Ethanol drinking decreased in the afternoon (Bin 2) and decreased further to near zero when the housing room lights were off (Bin 3). From just before the time that housing room lights turned on in the morning until the end of the 22‐h session (Bin 4), a small amount of ethanol consumption was sometimes observed.
FIGURE 3.

(A) Daily average of ethanol intake (g/kg) for each week over 6 months of open access. Data represent mean + or − SEM for males (filled circles) and females (open squares). (B) Cumulative open‐access ethanol intake.
FIGURE 4.

Hourly drinking patterns over the first (A) and second (B) month of open‐access drinking. Arrows indicate when meals were available. Shaded section of graph represents when lights were off in the housing room. Bins are indicated by vertical dotted lines. Males are represented by filled circles and females are represented by open squares. Data represent mean ± SEM.
FIGURE 5.

Proportion of ethanol consumed in each bin over the 6 months of open‐access drinking. Brackets at the top of the graph indicate each bin. Males (filled circles) drank significantly more during Bin 1 in Months 2–6. Females (open squares) drank significantly more during Bin 2 in Months 2–6. In Month 4, females also drank significantly more during Bin 4. *p < 0.05.
Figure 5 shows the average proportion of ethanol consumed in each of these four bins for each month of open‐access drinking. Analyses were performed to determine whether the proportion of ethanol consumed in each bin differed over time and between sexes. For Bin 1, a two‐way repeated‐measures ANOVA revealed a main effect of month [F(3, 30) = 3.417, p = 0.030] and sex [F(1,10) = 6.81, p = 0.026]. Post hoc Sidak multiple comparisons testing revealed that males drank a significantly higher proportion of their daily ethanol in Bin 1 than females in Months 2–6, but not Month 1. Bin 2 also showed a main effect of month [F (3,30) = 3.417, p = 0.030] and sex [F(1,10) = 6.806, p = 0.026]. Multiple comparisons revealed that, opposite to Bin 1, females drank a significantly higher proportion of their daily ethanol than males during Bin 2 in Months 2–6. Bins 3 and 4 showed no significant main effects; however, in Month 4 only, females drank a significantly higher proportion than males in Ben 4. For all differences found to be significant, effect sizes were determined to be large (Cohen's d > 1.0) except for the sex difference in Bin 4, Month 4, for which the effect size was moderate (d = 0.61).
DISCUSSION
The present studies characterized and compared ethanol‐drinking patterns in male and female cynomolgus monkeys during induction of ethanol drinking and throughout a subsequent 6 months of open‐access drinking. By utilizing this model of ethanol drinking, a range of voluntary open‐access (63–230 g/kg) and lifetime (152–320 g/kg) ethanol intakes were established across the 11 monkeys used in this study. The relationships between several characteristics of drinking during schedule induction and subsequent open‐access drinking were explored. Taken together, the data from these experiments indicate a lack of sex differences in drinking characteristics during the 1.5 g/kg phase of induction. However, when considered independent of sex, several characteristics predicted ethanol intake during the subsequent open access period, as had been observed previously (Grant et al., 2008). During open‐access drinking, sex differences in the daily pattern of ethanol consumption were observed.
Four behavioral variables describing ethanol drinking during induction were assessed for their ability to predict future drinking. Because there were no significant differences between males and females, data for all 11 monkeys were combined and regressions were performed to compare these characteristics with open‐access ethanol intake. Consistent with results reported by Grant et al. (2008), regressions revealed associations between three of the four induction variables (percent of dose consumed in the largest bout, number of pellets in State 1 and time to finish the 1.5 g/kg dose) and ethanol intake during 6 months of open access, expanding these predictor variables to include female subjects. The fourth variable, number of bouts, was negatively associated with higher open‐access ethanol intake, although the association did not reach statistical significance (p = 0.110). Qualitatively, this result is concordant with previous studies which have associated a lower number of bouts with a greater likelihood of heavy drinking (Baker et al., 2017; Grant et al., 2008). The lack of differences in male and female drinking characteristics during schedule induction may be related to the constraints on drinking inherent in the paradigm (e.g., daily cap on ethanol intake and limited session duration). A lack of sex differences during induction, therefore, does not preclude sex differences during the less constrained open‐access period which followed.
Studies in rodents frequently report higher ethanol consumption in females compared with males (Salazar & Centanni, 2024). In humans, however, males often have higher consumption (White, 2020). Importantly, data from both rodents and humans indicate that females are more vulnerable to the medical consequences of alcohol use (e.g., Salazar & Centanni, 2024). NHP data on sex differences in ethanol drinking are limited, but a 2003 review (Grant & Bennett, 2003) highlighted a few studies in which adult male old‐world monkeys drank more ethanol than females under several schedules of access that closely model human drinking. Baker et al. (2017) included females in their analysis of induction behaviors predicting future drinking, but low variability in ethanol consumption complicated a comparison of the sexes across ethanol intake levels. The present data set contains both males and females with a range of ethanol intakes. Males and females responded in qualitatively different ways to the transition from the tightly controlled, limited‐access conditions during induction to the near‐unlimited ethanol availability during open access. During the first week, females' average ethanol intake decreased by ~56% (from 1.44 ± 0.07 to 0.63 ± 0.43 g/kg) and gradually recovered over the next 10–13 weeks. Males, on the other hand, displayed a smaller decrease in drinking during the first week of open access (41%, from 1.46 ± 0.05 to 0.86 ± 0.28 g/kg) and returned to levels of drinking observed at the end of induction in the second week of open access. Moreover, when comparing weekly ethanol consumption over 6 months, males drank more ethanol on average, as has been observed in some previous studies (Fahlke et al., 2000; Vivian et al., 2001). However, there was no main effect of sex over 6 months of open‐access drinking, and post‐hoc multiple comparisons tests demonstrated no single week in which males drank significantly more than females.
Analysis of daily patterns of ethanol consumption during open access revealed sex differences in the distribution of ethanol intake across the day. For both males and females, the general pattern of drinking consisted of peaks in the first, third and fifth hours of the session when meals were available, some afternoon drinking before the housing room lights were extinguished, no drinking while lights were off and a small amount of morning drinking just before and after lights in the housing room were turned on. This pattern was consistent throughout the 6 months of open‐access ethanol drinking. However, male monkeys consumed a much greater proportion of their daily ethanol intake during meals compared with females. Once males had consumed their daily food ration (at the end of Bin 1), drinking declined toward zero. Females on the contrary, spread their intake out across the first 9 h of the session (Bins 1 and 2). This pattern was exacerbated in Month 2 of open access as males drank an even greater proportion of their daily ethanol in Bin 1 vs. Bin 2, whereas the females' drinking in Month 2 was similar to Month 1. These sex differences continued through the remaining 5 months of open access (Figure 5). Thus, the proportion of ethanol consumed in Bin 1 and Bin 2 was significantly different between the sexes in Months 2 through 6. No monkeys consumed an appreciable amount of ethanol during the lights‐off period, aligning with previous literature that indicates only heavy drinkers (>3.0 g/kg/day ethanol) typically drink during the night and into the morning (Grant et al., 2008; Vivian et al., 2001). Females were slightly more likely to consume ethanol in the morning, but this difference was significant only in Month 4.
The sex difference in the distribution of ethanol intake across the day may be the result of a sex difference in a phenomenon termed front loading: a drinking pattern in which ethanol intake is most rapid just after the start of the access period. Although few studies have examined sex differences in front loading, the phenomenon was more likely to be observed in female rodents than in male rodents (Bauer et al., 2021; Flores‐Bonilla et al., 2021; McNamara et al., 2025), However, in these studies, differences dissipated when the session was shortened or when the response requirement was increased (Bauer et al., 2021; Flores‐Bonilla et al., 2021), suggesting that sex differences in front loading are not observed under all conditions of ethanol availability. Nonetheless, the limited available data suggest that the direction of sex differences in front loading, like in total ethanol intake per session, is opposite in rodents vs. NHPs. Another possible explanation for the differential distribution of ethanol intake across the day may involve sex differences in vulnerability with respect to the circadian cycle, suggesting that time of day or certain cues (in this case, food availability) can increase vulnerability for ethanol drinking differently in male and female NHPs.
This study has some limitations that should be addressed. First, variables of interest were chosen based on data collected from only male subjects. It is possible that the conclusions based on all‐male data do not extend to a female‐only or mixed‐sex data set. To address this, we conducted a PCA and PCR using as many of the variables used by Grant et al. (2008) as possible, plus the time to finish the 1.5 g/kg dose (see Supplemental Materials). Our PCA revealed no clustering of the sexes and determined that principal component 1 (PC1) accounted for 70.65% of variance (Figure S1). The PCR showed a significant relationship between PC1 and subsequent open‐access EtOH intake (Figure S2). Of the seven variables we included in our PCA analyses, the four variables described in Figures 1 and 2 had the highest absolute value loading scores (>0.960), followed closely by EtOH drinks/bout (−0.856), then water bouts (−0.534) and lastly water drinks/bout (−0.385). Unpaired t‐tests showed no significant differences between males and females for the variables not shown in Figure 1 or 2 (Figure S3). Simple linear regressions comparing open‐access ethanol intake and these variables revealed a significant relationship between intake and ethanol drinks/bout, but not water bouts or water drinks/bout (Figure S4). The results of these analyses support the contention that variables shown to be predictive of later ethanol drinking in a male‐only data set are also predictive in a mixed‐sex data set. Future research into potential sex differences in the predictability of induction behaviors should include more subjects per sex. It is also possible that the earlier phases of induction may be predictive for females, despite not being predictive for males by Grant et al. (2008). This is unlikely however, as inspection of data from earlier phases of induction in the present study did not demonstrate variability between male and female subjects (not shown). Other limitations in this study include the focus on only 6 months of open‐access drinking compared with 12 months in Grant et al. (2008). Furthermore, the number of subjects for each sex is relatively low. However, an a priori power analysis and post hoc sensitivity analysis determined that the present study was adequately powered to detect an effect size as low as 0.23, where 0.2, 0.5 and 0.8 indicate a small, medium and large effect, respectively.
FUNDING INFORMATION
This work was supported by a grant from the National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism (R01 AA027556).
CONFLICT OF INTEREST STATEMENT
None of the authors have a conflict of interest to disclose.
Supporting information
Figures S1–S4
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
REFERENCES
- Baker, E.J. , Walter, N.A.R. , Salo, A. , Rivas Perea, P. , Moore, S. , Gonzales, S. et al. (2017) Identifying future drinkers: behavioral analysis of monkeys initiating drinking to intoxication is predictive of future drinking classification. Alcoholism, Clinical and Experimental Research, 41(3), 626–636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauer, M.R. , McVey, M.M. & Boehm, S.L., II . (2021) Three weeks of binge alcohol drinking generates increased alcohol front‐loading and robust compulsive‐like alcohol drinking in male and female C57BL/6J mice. Alcoholism, Clinical and Experimental Research, 45(3), 650–660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fahlke, C. , Lorenz, J.G. , Long, J. , Champoux, M. , Suomi, S.J. & Higley, J.D. (2000) Rearing experiences and stress‐induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates. Alcoholism, Clinical and Experimental Research, 24(5), 644–650. [PubMed] [Google Scholar]
- Fama, R. , Le Berre, A.‐P. & Sullivan, E.V. (2020) Alcohol's unique effects on cognition in women: a 2020 (re)view to envision future research and treatment. Alcohol Research: Current Reviews, 40(2), 3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores‐Bonilla, A. , De Oliveira, B. , Silva‐Gotay, A. , Lucier, K.W. & Richardson, H.N. (2021) Shortening time for access to alcohol drives up front‐loading behavior, bringing consumption in male rats to the level of females. Biology of Sex Differences, 12, 51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores‐Bonilla, A. & Richardson, H.N. (2020) Sex differences in the neurobiology of alcohol use disorder. Alcohol Research: Current Reviews, 40(2), 4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galbo, L.K. , Davenport, A.T. , Epperly, P.M. , Daunais, J.B. , Stinson, B.T. & Czoty, P.W. (2022) Social dominance in monkeys: lack of effect on ethanol self‐administration during schedule induction. Alcohol, 98, 1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galbo‐Thomma, L.K. , Davenport, A.T. , Epperly, P.M. & Czoty, P.W. (2023) Influence of social rank on the development of long‐term ethanol drinking trajectories in cynomolgus monkeys. Alcoholism, Clinical and Experimental Research, 47(10), 1943–1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goonawardena, A.V. , Morairty, S.R. , Orellana, G.A. , Willoughby, A.R. , Wallace, T.L. & Kilduff, T.S. (2018) Electrophysiological characterization of sleep/wake, activity and the response to caffeine in adult cynomolgus macaques. Neurobiology of Sleep and Circadian Rhythms, 6, 9–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grant, K.A. & Bennett, A.J. (2003) Advances in nonhuman primate alcohol abuse and alcoholism research. Pharmacology & Therapeutics, 100(3), 235–255. [DOI] [PubMed] [Google Scholar]
- Grant, K.A. , Leng, X. , Green, H.L. , Szeliga, K.T. , Rogers, L.S.M. & Gonzales, S.W. (2008) Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self‐administration. Alcoholism, Clinical and Experimental Research, 32(10), 1824–1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McNamara, T.A. , Weng, H. , Liao, H.Y. & Ito, R. (2025) Individual and sex differences in frontloading behavior and approach‐ avoidance conflict preference predict addiction‐like ethanol seeking in rats. Scientific Reports, 15, 2982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) . (2024) Alcohol use disorder (AUD) in the United States: age groups and demographic characteristics, September . Available from: https://www.niaaa.nih.gov/alcohols‐effects‐health/alcohol‐topics/alcohol‐facts‐and‐statistics/alcohol‐use‐disorder‐aud‐united‐states‐age‐groups‐and‐demographic‐characteristics [Accessed 3rd January 2026].
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) . (2025) Alcohol use in the United States: age groups and demographic characteristics, February . Available from: https://www.niaaa.nih.gov/alcohols‐effects‐health/alcohol‐topics‐z/alcohol‐facts‐and‐statistics/alcohol‐use‐united‐states‐age‐groups‐and‐demographic‐characteristics [Accessed 3rd January 2026].
- Phillips, K.A. , Bales, K.L. , Capitanio, J.P. , Conley, A. , Czoty, P.W. , ‘t Hart, B.A. et al. (2014) Why primate models matter. American Journal of Primatology, 76(9), 801–827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sacks, J.J. , Gonzales, K.R. , Bouchery, E.E. , Tomedi, L.E. & Brewer, R.D. (2015) 2010 National and State costs of excessive alcohol consumption. American Journal of Preventive Medicine, 49(5), e73–e79. [DOI] [PubMed] [Google Scholar]
- Salazar, A.L. & Centanni, S.W. (2024) Sex differences in mouse models of voluntary alcohol drinking and abstinence‐induced negative emotion. Alcohol, 121, 45–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slade, T. , Chapman, C. , Swift, W. , Keyes, K. , Tonks, Z. & Teesson, M. (2016) Birth cohort trends in the global epidemiology of alcohol use and alcohol‐related harms in men and women: systematic review and metaregression. BMJ Open, 6(10), e011827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Towers, E.B. , Williams, I.L. , Qillawala, E.I. , Rissman, E.F. & Lynch, W.J. (2023) Sex/gender differences in the time‐course for the development of substance use disorder: a focus on the telescoping effect. Pharmacological Reviews, 75(2), 217–249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vivian, J.A. , Green, H.L. , Young, J.E. , Majerksy, L.S. , Thomas, B.W. , Shively, C.A. et al. (2001) Induction and maintenance of ethanol self‐administration in cynomolgus monkeys (Macaca fascicularis): long‐term characterization of sex and individual differences. Alcoholism: Clinical and Experimental Research, 25, 1087–1097. [PubMed] [Google Scholar]
- Weerts, E.M. , Fantegrossi, W.E. & Goodwin, A.K. (2007) The value of nonhuman primates in drug abuse research. Experimental and Clinical Psychopharmacology, 15, 309–327. [DOI] [PubMed] [Google Scholar]
- White, A.M. (2020) Gender differences in the epidemiology of alcohol use and related harms in the United States. Alcohol Research: Current Reviews, 40(2), 01. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figures S1–S4
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
