Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

Abstract Background Factors leading to the harmful consumption of substances, like alcohol and sucrose, involve a complex interaction of genes and the environment. While we cannot control the genes we inherit, we can modify our environment. Understanding the role that social and environmental experiences play in alcohol and sucrose consumption is critical for developing preventative interventions and treatments for alcohol use disorders and obesity. Methods We used the drinking in the dark two‐bottle choice (2BC) model of ethanol and sucrose consumption to compare male C57BL/6 mice housed in the IntelliCage (an automated device capable of simultaneously measuring behaviors of up to 16 mice living in an enriched social environment) with mice housed in standard isolated and social environments. Results Consistent with previous publications on ethanol‐naïve and ‐experienced mice, social and environmental enrichment reduced ethanol preference. Isolated mice had the highest ethanol preference and IntelliCage mice the least, regardless of prior ethanol experience. In mice with no prior sucrose experience, the addition of social and environmental enrichment increased sucrose preference. However, moving isolated mice to enriched conditions did not affect sucrose preference in sucrose‐experienced mice. Conclusions The impact of social and environmental enrichment on ethanol consumption differs from sucrose consumption suggesting that interventions and treatments developed for alcohol use disorders may not be suitable for sucrose consumption disorders.

and as such, understanding the role that social and environmental experiences play in the consumption of alcohol and sugar is critical for developing preventative interventions and treatments.
In AUDs, daily life experiences (like people, places, smells, meal rituals, and stress) form cues which become associated with alcohol consumption, and subsequent exposure to these cues increases the amount of alcohol consumed during drinking bouts and impedes the ability to remain abstinent (for reviews see, Breese, Sinha, & Heilig, 2011;Little et al., 2005;Sinha & Li, 2007). Similarly, environmental cues can also influence the consumption of sugary foods (Burger & Stice, 2014;Grenard et al., 2013;Hattersley, Irwin, King, & Allman-Farinelli, 2009;Schmidt, Voorn, Binnekade, Schoffelmeer, & De Vries, 2005). To date, the majority of preclinical research investigating the impact of social and environmental enrichment on ethanol and sucrose consumption has been directed toward ethanol consumption (see Tables 1 and 2). While there is considerable methodological variation between the models used in these studies (species, strain, ethanol concentration, type and length of ethanol access), they generally show that social deprivation (individual rather than group housing) increases ethanol consumption (Lodge & Lawrence, 2003;Schenk, Gorman, & Amit, 1990;Wolffgramm, 1990;Wolffgramm & Heyne, 1991). The role of other types of environmental enrichment designed to provide physical and/or cognitive stimulation is less clear. Studies in two different rat strains suggest that providing a combination of social and environmental enrichment causes an increase in ethanol consumption (Rockman, Gibson, & Benarroch, 1989;. In contrast, another study found that environmentally enriched-socially deprived and socially enriched-environmentally deprived female C57BL/6 mice consumed less ethanol than socially and environmentally deprived counterparts (Pang et al., 2013). Interestingly, the  (2003) Rat Wistar ♂ 20 2BC, 24 hr, 9 months S < C < I StoI>I Wolffgramm (1990) Rat Long Evans ♂ 10 Intermittent 2BC, 24 hr, 37 days Early: S < I b Late: S = I Schenk et al. (1990) S, group housing; I, individual housing; EI, individual housing and enrichment; E, group housing and enrichment; S(P), alcohol preferring in group housing; S(NP), nonalcohol preferring in group housing; C, sensory without physical contact in single housing. a Effect significant for bout duration in juvenile but not adult mice. b Housed individually from P21 (Early) or P60 (Late). studies by Rockman and colleagues (Rockman et al., 1989) and Pang and colleagues (Pang et al., 2013) found no difference in ethanol consumption between socially enriched-environmentally deprived and environmentally enriched-socially deprived rats and mice, respectively. While there are differences in sex, strain, and methodology in the above studies, which could explain the contrasting effects of combined social and environmental enrichment on ethanol consumption, it is established that social and environmental factors are important determinants of ethanol consumption in rodents.

T A B L E 2 Sucrose consumption and social and environmental enrichment
In recent years, it has been shown that the consumption of sucrose can lead to behavioral changes which meet addiction criteria defined in the Diagnostic and Statistical Manual V (DSM-V) (American Psychiatric Association, 2013) (for reviews see, Hoebel, Avena, Bocarsly, & Rada, 2009;Avena, 2007;Avena, Rada, & Hoebel, 2008), and influences the same reward pathways in the brain as substances of abuse, like nicotine (De Vries, de Vries, Janssen, & Schoffelmeer, 2005), ethanol (Steensland et al., 2010), opioids (Spangler et al., 2004), and cocaine (Lenoir, Serre, Cantin, & Ahmed, 2007). While many of the characteristic of sucrose consumption are like ethanol consumption, very little research has been directed toward investigating the role of social and environmental factors in sucrose consumption (see Table 2). With the exception of one study (Grimm et al., 2008) focusing on relapse behavior rather than the development and maintenance of sucrose consumption; the currently available research suggests neither social nor environmental nor a combination of these factors influence sucrose consumption (Brenes & Fornaguera, 2008;Hall, Humby, Wilkinson, & Robbins, 1997;Moles & Cooper, 1995). It remains, however, undetermined whether moving rats from deprived environments to enriched environments and vice versa impacts subsequent sucrose consumption, similar to ethanol consumption. If indeed social and environmental factors are not important for specific aspects of sucrose consumption behavior, this feature would make sucrose consumption unique to other substances of abuse, like morphine, cocaine, nicotine, and ethanol (Wolffgramm, 1990;Alexander, Beyerstein, Hadaway, & Coambs, 1981;Gipson, Beckmann, El-Maraghi, Marusich, & Bardo, 2011;Mesa-Gresa, Ramos-Campos, & Redolat, 2013), and could be utilized to, not only, improve our understanding and treatment of AUDs (and other addictions), but also to enhance our understanding of the factors which drive excessive sucrose consumption and our ability to prevent and treat obesity.
In this study, we used the drinking in the dark (DID) two-bottle choice (2BC) procedure (Rhodes, Best, Belknap, Finn, & Crabbe, 2005) to model ethanol and sucrose consumption in mice and compared the effect of social (S) and social plus environmental enrichment (E) with social and environmental deprivation (I). The DID 2BC procedure is most commonly used to model excessive binge-like ethanol consumption in mice for studying the underlying mechanisms of ethanol consumption disorders and identifying potential novel therapeutics (e.g., see Fritz et al., 2014;Gritz, Larson, & Radcliffe, 2016;Patkar et al., 2017). More recently, it has been adapted for studying excessive binge-like sucrose consumption (e.g., see Steensland et al., 2010;Patkar et al., 2017;Dhaher et al., 2009). It should be noted that the model of sucrose consumption described in this study is different to the model of sucrose consumption commonly used for measuring depression-like behaviors. The later model generally involves administering lower concentrations of sucrose to mice for short periods (once weekly or for a few days at a time) (e.g., see Benturquia et al., 2007;Covington, Vialou, LaPlant, Ohnishi, & Nestler, 2011;Ho et al., 2016). However, the DID model generally uses higher sucrose concentrations which are administered for long periods of time (daily for weeks to months) (e.g., see Fritz et al., 2014;Gritz et al., 2016;Patkar et al., 2017). Models utilizing long-term administration of sucrose are not suitable for measuring depression-like behaviors as they produce morphological changes within the brain . As the space available for free movement in the standard mouse cage was limited during standard group housing conditions, the addition of enrichment to the standard sized cage, which would have further reduced the living space available, was undesirable. Living in cramped conditions creates stress and could potentially confound any positive effects obtained from the provision of enrichment (Lin et al., 2015). To avoid this issue, we used the

| Animals and housing
Male 5
Mice were given access to one bottle of water and one bottle of 20% (v/v) ethanol or 5% (w/v) sucrose in their home cage environment for were not able to be rehoused in groups in the standard 2BC cages due to excessive aggressive behavior. These mice were instead group housed in the IntelliCage (IE) and vice versa (EI). For sucrose, 18 mice were group housed in six cages and 18 mice were individually housed.
For ethanol, 27 mice were group housed in nine cages and 12 mice were individually housed.

| IntelliCage 2BC
The IntelliCage is an automated device which can track the individual behaviors of up to 16 mice simultaneously via subcutaneously implanted transponders. The IntelliCage (20 × 55 × 38 cm) contained four standard cubby houses in the center of the arena and four automated cubby houses, one per corner. Antennas at the entrance to each automated corner allowed the IntelliCage to track how many visits each mouse made to each corner and how long they spent in each corner via the transponders. A temperature sensor confirmed that the mouse was present in the corner and infrared beams monitored nosepokes to each drinking port. A lickometer recorded the number of licks to each sipper tube. The automated cubby houses also contained access holes for two bottles, with cue lights above the access holes.
Each mouse had a transponder implanted subcutaneously, under isofluorane anesthesia, between the shoulder blades 3 days before drinking sessions commenced. During the nontest period, the access port to the ethanol/sucrose bottle was closed and the cue lights were off.
The room lights were on a 12 hr reverse light cycle and turned off at 11 am. The drinking sessions commenced at 2 pm, at which point the cue lights turned on and the door to the ethanol/sucrose port opened.
Two hours later, the access port to the ethanol/sucrose bottle was F I G U R E 1 Experimental timeline. Following a habituation period, mice housed individually, in groups of 3-5 or in groups of 12 in the IntelliCage, consumed 20% (v/v) ethanol for 18 sessions (a) or 5% (w/v) sucrose for 15 sessions (b) using the drinking in the dark paradigm. Immediately following the last drinking session, the housing environments were changed. Approximately 3 days later, the mice recommenced drinking sessions for seven more sessions. After every fifth session, mice has access to water only for 2 days periments. Due to computer malfunction, the data from days 7, 9, and 13-15 for E mice consuming sucrose ( Figure 4) were not saved. The computer malfunction did not affect the operation of the IntelliCage, only the transfer of data, and as such access to sucrose during the drinking session on these days was not affected.

| Statistics
Statistical analysis was performed using GraphPad Prism software (version 6, USA) and all results are expressed as mean ± standard error of the mean (SEM). Ethanol and sucrose preference under the different housing conditions were compared using ordinary two-way ANOVA with Bonferroni's post hoc test, except when analyzing the effect of switching the housing conditions in the isolated to social and social to isolated groups that were drinking ethanol. A one-way ANOVA with Bonferroni's post hoc test was used as data could not be collected for the post-housing switch period for the isolated to social group. For the analysis of the data presented in Figure 4, all the data collected on days 7, 9, and 13-15 (corresponding to the IntelliCage computer malfunction for sucrose-consuming mice) were excluded from the analysis.

| The effect of social and environmental enrichment on ethanol consumption
To determine whether ethanol consumption could be modulated by manipulating social and environmental conditions, we compared the preference for ethanol over water from mice living in single housing without enrichment (I), group housing without enrichment (S), and group housing with enrichment (IntelliCage, E

| Environmental enrichment does not influence preference in sucrose-experienced mice
Finally, to determine whether the removal or addition of social interaction impacts sucrose preference in mice with previous sucrose experience, we rehoused I mice in groups of three per cage (IS) and S in individual cages (SI) ( Figure 5). As the aggressive behavior demonstrated by the ethanol mice was not observed in the sucrose mice, and we found no difference in sucrose preference in S and E mice in the previous experiment, we recommenced the drinking sessions in both groups of mice after a 3-day habituation period using standard cages only. Analysis with two-way ANOVA and Bonferroni's post hoc test showed no interaction of drinking session and housing condition on sucrose preference (F(7,172)=2.005, p = .057), no effect of housing condition (F(1,172)=2.481, p = .117) but an effect of drinking session alone (F(7,172)=7.357, p < .0001). The average sucrose preference of the IS mice was 89.71 ± 1.711 and 90.57 ± 1.956% and the SI mice was 94.46 ± 0.877 and 91.56 ± 1.183% before and after the housing switch, respectively.

| DISCUSSION
In this study, we examined the effect of social and environmental enrichment on ethanol and sucrose consumption. We show that ethanol preference increases with social and environmental deprivation and that this increase in preference can be reversed with the provision of social and environmental enrichment. Additionally, we found that ethanol preference is inversely proportional to the level of environmental enrichment provided implying social and cognitive interactions are more rewarding than the pharmacological effects of ethanol. Our findings for ethanol preference are consistent with previous publications (see Table 1) and a study by Sampson and colleagues showing that rats are willing to do more work to obtain a sucrose reward compared to an ethanol reward (Samson, Slawecki, Sharpe, & Chappell, 1998). Pang and colleagues demonstrated that the provision of social or environmental enrichment reduces ethanol consumption in female C57BL/6 mice (Pang et al., 2013). Wolffgramm and colleagues produced a similar result in male Wistar rats (Wolffgramm, 1990). They allowed sensory contact (sight, smell, vocal communication) without physical contact by placing a perforated divider in the cage and housing a rat on either side of the divider. The rats with sensory contact consumed more ethanol than group-housed rats but less than individually housed rats.
Conversely, Rockman and colleagues found the concurrent addition of social and environmental enrichment increased ethanol consumption in Wistar and Sprague Dawley rats (Rockman et al., 1989;Rockman, Borowski, & Glavin, 1986). Extending on these findings, they showed that rats moved to an enriched environment drank similar amounts of ethanol to rats remaining in isolation and more than the rats moved from an enriched to a deprived environment, while the rats remaining in the enriched environment drank the most ethanol (Rockman et al., 1989). Interestingly, a study by Juarez and Vazquez-Cortes showed that when ethanol is offered in an isolated setting, rats normally housed I, S, IS, or SI drink similar amounts of ethanol (Juarez & Vazquez-Cortes, 2003  While the later studies appear to conflict with our findings and the previous studies (demonstrating rodents in isolation consume more ethanol than socially housed animals), further examination of the methodology used indicates that they may actually support the finding of this and former studies. The studies by Rockman and Juarez and Vazquez-Cortes, all involved altering the housing environments of ethanol-experienced rats. In each of these studies, rehousing ethanolexperienced rats in a social setting produced an increase in ethanol consumption; whereas the former studies were performed in ethanolnaive animals. From previous rodent research, we know that changes to housing conditions are stressful for rodents (Misslin, Herzog, Koch, & Ropartz, 1982;Tuli, Smith, & Morton, 1995), rodents in an isolated housing environment are more sensitive to stress than those in a social environment (Giralt & Armario, 1989), stress alters ethanol consumption (Cozzoli, Tanchuck-Nipper, Kaufman, Horowitz, & Finn, 2014;Meyer, Long, Fanselow, & Spigelman, 2013), ethanol experience alters ethanol reward value (Shimizu et al., 2015;McCusker & Bell, 1988), and ethanol consumption reduces the ability to cope with stress (Zhao, Weiss, & Zorrilla, 2007). Taken together, one could argue that for ethanol-naïve rats, the provision of social interactions provides greater rewarding benefits/stress relief than the biological effects obtained from ethanol consumption. But for ethanol-experienced rats, moving into a socially and cognitively enriched setting appears to be stressful, and the rewarding benefits/stress relief from the biological effects of ethanol is perceived to outweigh those obtained from engaging in social and environmental interactions.
It is difficult to say whether the same could be said for mice.
Certainly, we were unable to rehouse ethanol-experienced mice into groups due to aggressive behavior, and it could be that the aggressive behavior indicated that the ethanol-experienced mice had a reduced capacity to cope with the changes in housing conditions since stress can increase aggressive behavior in mice (Yang et al., 2015). However, we were able to rehouse the ethanol-experienced mice in a social environment with the IntelliCage. Most likely, the additional space per animal allowed greater capacity to escape aggressive/stressful challenges and the cognitive stimulation provided distraction from the stress created by the change to housing conditions. However, further studies are required to explore these possibilities.
In this study, we also demonstrate that social and environmental enrichment plays a different role in sucrose and ethanol consumption.
Increasing enrichment produced a reduction in ethanol preference in both the naïve and ethanol-experienced animals. However, in naïve mice, providing enrichment increased sucrose consumption, whereas the amount of enrichment provided had no effect on sucrose preference in sucrose-experienced mice. Broadly, consumption behaviors can be broken down into different phases: acquisition, maintenance, withdrawal, and relapse (for reviews see, Bhutada et al., 2012;Carroll, 1993;Marchant, Li, & Shaham, 2013;Robinson, Khurana, Kuperman, & Atkinson, 2012). In this study, the ethanol preference of the naïve mice was measured during the acquisition and maintenance phases, whereas the ethanol preference of the experienced mice was measured during the maintenance phase only. This suggests that social and environmental enrichment may be important for acquisition but not maintenance of sucrose consumption; differing from ethanol consumption where both acquisition and maintenance were modulated by social and environmental enrichment. It also suggests that (in these circumstances) the reward benefits/stress relief gained from sucrose consumption outweigh those obtained from social and environmental interaction, particularly during the maintenance phase of sucrose consumption. That is, sucrose may be more addictive than ethanol.
In support of this hypothesis, Sampson and colleagues measured the breakpoint in rats responding for ethanol and sucrose (Samson et al., 1998). They found that a higher percentage of rats would press the lever at breakpoint (32 lever presses for a single reward delivery) for sucrose (~80%) than ethanol (~40%).
Along the same lines, it is also possible that greater levels of stress are required to increase sucrose consumption during the maintenance phase. Supporting this, Grimm and colleagues (Grimm et al., 2013) found that following 29 days of withdrawal from sucrose, rats which experienced social interactions lever pressed for sucrose more than rats housed in isolation. Additionally, Gill and Cain demonstrated that under normal feeding conditions, environmentally enriched Sprague Dawley rats lever pressed for sucrose rewards less than those housed individually (Gill & Cain, 2011). However, under more stressful conditions (when the rats were deprived of food) the environmentally enriched rats pressed for sucrose more than the deprived rats.

Interestingly, McCool and Chappell found socially housed Long
Evans rats' lever pressed for sucrose more than isolated rats, but following a single day of extinction training, no difference could be found (McCool & Chappell, 2009) In another study, Van den Berg and colleagues demonstrated that single-housed rats have greater conditioned place preference for sucrose than socially housed rats ( Van den Berg et al., 1999). These rats did not have prior experience with sucrose, nor were they provided with enrichment or subjected to stress, which could explain why these findings are similar to sucrose responding under non-food deprived conditions (Gill & Cain, 2011). Experiments exploring the effects of stress on conditioned place preference in sucrose-naïve and -experienced rat housed in enriched and deprived environments are required to clarify how these factors influence sucrose consumption behaviors. However, it is clear that the relationship between social and environmental interactions and consumption behaviors is complex and more research is required to understand how these factors are specifically involved in sucrose consumption.
It is noteworthy that in this study, the mice (regardless of the housing conditions) consume sucrose almost exclusively when offered a choice between sucrose and water. Srisontiyakul and colleagues have shown that in order to match lever responding in an operant setting for 10% ethanol, they had to reduce the concentration of sucrose from 5% to 0.3-1% (Srisontiyakul, Kastman, Krstew, Govitrapong, & Lawrence, 2016). The literature on sucrose consumption is quite diverse, with reported sucrose concentrations used for consumption studies varying from 0.3% to 35%. The most commonly reported concentrations are 5 and 10% sucrose. We chose 5% over 10% based on Srisontiyakul's study, to allow comparisons with our previous publications showing that long-term consumption of 5% sucrose using the IA2BC model alters nucleus accumbens morphology  and our studies showing the 5% concentration can be used to test novel compounds for their ability to reduce bingelike sucrose consumption (Steensland et al., 2010;Patkar et al., 2017;Nielsen et al., 2008;Shariff et al., 2016;Simms, Haass-Koffler, Bito-Onon, Li, & Bartlett, 2012;Simms et al., 2011;Srinivasan et al., 2012).
While it is possible that the preference for sucrose represents a celling value and reducing the sucrose concentration may enable further dissection of the factors which lead to increased consumption of sucrose, it is more likely that sucrose consumption, regardless of the concentration consumed, is not significantly modulated by social and environmental conditions. Hall and colleagues found socially and individually housed rats consumed similar amounts of 0.7, 2.1, 7.0, 21.0, and 34.0% sucrose solutions (Hall et al., 1997). However, this aspect remains to be explored.
It is also important to address the reduced ethanol consumption of EI mice during sessions 5 and 6 post housing switch (Figure 3a). It is unclear whether this reduction is an artifact or a reflection of biological or social structure changes. Based on previous studies within our laboratory, it is not unusual during the first 2 weeks of ethanol exposure to see ethanol-inexperienced mice, which initially consume ethanol at high levels, reduce their consumption for a day or two before returning to high levels of consumption. A similar dip in ethanol consumption can also be seen in Figure 1 of Rhodes' study (Rhodes et al., 2005) and in figure 2A of Matsons' study (Matson, Kasten, Boehm, & Grahame, 2014). Together, this implies that the reduced consumption is most likely biological in nature and unrelated to disturbances within the animal facility or experimental protocol. However, it is unclear what mechanisms may underlie this phenomenon. The most likely explanation is that the mice (temporarily) reduce their ethanol consumption due to the negative/aversive effects produced by repetitive daily binge-like ethanol consumption prior to the development of tolerance. Supporting this possibility, Carnicella and colleague demonstrated a u-shaped ethanol dose response curve in rats' lever pressing for access to ethanol (Carnicella, Yowell, & Ron, 2011). Specifically, the rats progressively increased their response for ethanol until the ethanol concentration reached 10-20%, and as the concentration increased beyond this point, their responding progressively decreased.
Additionally, a study by Linsenbart and colleagues shows that mice consuming ethanol using the DID model had more hind foot slips on the balance beam on day 8 than mice consuming water; but by day 15, the number of hind foot slips was similar to water-consuming mice (Linsenbardt, Moore, Griffin, Gigante, & Boehm, 2011), suggesting that the mice developed tolerance to ethanol sometime before the 15th day of exposure.
It should also be noted that we included a habituation period prior to commencing DID sessions and immediately following changes to housing conditions. The mice did not have access to their reinforcer during this time and it is possible that including a habituation period may have masked an effect of the housing switch, especially for sucrose intake. Certainly, there would be effects of the condition change on consumption during this period, had the mice has access to their reinforcer. However, it would be extremely difficult to dissect these effects from those produced by novelty and behaviors related to the reestablishment of social hierarchies. In this study, we chose to include a habituation period for three reasons. The first is primarily an ethical consideration: we wanted to ensure the wellbeing of the animals.
Taking rodents from social to isolated housing and from isolation into a social environment is very stressful and we needed to ensure there were no adverse wellbeing effects which could reduce consumption and confound our interpretation of the results. Secondly, we did not want the behaviors related to establishment of new social hierarchy, responses to novelty, the potential for fretting and appetite disturbances, and so on, produced by the initial change in housing conditions to interfere with the reestablishment of consumption behaviors.
Thirdly, we gave the mice an adaption period prior to commencing the pre-housing change drinking sessions and, as a control, wanted to match the conditions of the pre-and post-housing change drinking period as closely as possible. While the experimental conditions of this study were not suitable for studying consumption behaviors immediately after the housing switch, it would be possible to examine these aspects by making more subtle changes to the housing environment, like gradually increasing or decreasing the size of the cage, the number of mice in the cage or the amount of enrichment provided. It will be interesting to see the results of such studies in the future.
Research has shown that long-term binge-like consumption of ethanol  and sucrose  alter the structure of the brain and exposure to adverse environments during childhood significantly increase the risk of developing alcoholism and obesity (and other disorders) in later life (Brady & Back, 2012;Daoura, Haaker, & Nylander, 2011;Enoch, 2012). Certainly, epidemiological studies show that those living in a lower socioeconomic environments are more likely to be impacted by harmful alcohol consumption and/or obesity (Batty, Lewars, Emslie, Benzeval, & Hunt, 2008;McCartney et al., 2016;Ferraro, Schafer, & Wilkinson, 2016;Non et al., 2016). While the mechanisms underlying the detrimental neural effects of ethanol and sucrose remain unclear, the provision of environmental enrichment has been shown to be neuroprotective in rodents (Anastasía, Torre, de Erausquin, & Mascó, 2009;Barone, Novelli, Piano, Gargini, & Strettoi, 2012;Griñan-Ferré et al., 2016;Kiss et al., 2013;Livingston-Thomas et al., 2016).

| CONCLUSIONS
The IntelliCage system was a useful and versatile device for examining the involvement of social and environmental enrichment in consumption behaviors in mice. We demonstrated that the addition of social and environmental enrichment had different effects on ethanol and sucrose consumption behaviors in male C57BL/6 mice. The addition of enrichment reduced ethanol consumption in ethanol-naïve and -experienced mice and increased sucrose consumption in sucrosenaïve but not -experienced mice. While we can take advantage of these differences to advance our understanding of the mechanisms involved in the different phases of consumption disorders, we also need to carefully consider these factors when developing novel therapies. The behavioral characteristics of sucrose consumption are different from ethanol consumption, suggesting that treatment approaches similar to that used for AUDs may not be appropriate for controlling excessive sugar consumption.

ACKNOWLEDGMENTS
We wish to thank Dr Arnauld Belmer for his editorial advice.