Sugar consumption induces the consummatory suppression of sugary ethanol: Differential effects of sugar restriction according to sex and age

Preference for sweet-tasting flavors has evolutionary roots because they represent a high source of energy and have a positive hedonic value (Martire et al., 2013); however, in recent decades, the increase in sugar consumption, especially in the form of sweetened beverages, has become a major human health problem and is associated with the use of other palatable, caloric, or addictive substances (Treur et al., 2016).

The increased consumption of substances like sugar involves the activity of the reward system. This system is crucial for processing natural reinforcers, and it is also abnormally recruited when addictive substances are consumed (Fortuna, 2010, Morales et al., 2020, Pfarr et al., 2018). During adolescence, humans and rodents experience maturational changes in their reward systems; these changes heighten impulsivity and risk-seeking behaviors that contribute to the early use of drugs, such as ethanol (Balogh et al., 2013, Saalfield and Spear, 2016). Studies have also reported higher ethanol consumption in adolescent and adult rats. For example, ad libitum access to sweetened or unsweetened alcohol solutions for several days increased preference and intake in adolescent male and female rats compared to adults. Particularly, in a 20-hour, two-bottle-choice paradigm between water and sweetened ethanol (10% EtOH + 0.1% saccharin), adolescent rats of both sexes consumed more ethanol than adults over a 10-day period (Doremus et al., 2005). Moreover, in a 23-hour, two-bottle-choice paradigm between water and sweetened (10% EtOH + 0.1% saccharin) or unsweetened ethanol (10%), adolescent rats preferred and consumed significantly more ethanol (g/kg) than adults, regardless of whether the ethanol was sweetened or not (Doremus et al., 2005, Vetter et al., 2007). Adolescent rats of both sexes also exhibited higher preference and ethanol intake than their adult counterparts when subjected to an intermittent schedule consisting of two-hour access windows to sweetened ethanol (6% EtOH + 0.1% saccharin) for four days, followed by access to a more concentrated mixture (10% EtOH + 0.1% saccharin) for another four days (Vetter-O’Hagen et al., 2009). Furthermore, earlier research suggests that ethanol consumption during adolescence facilitates consumption in adulthood. In this sense, male adolescent rats (postnatal days (PND): 26-59) that had access to 20% ethanol for three days a week followed by a four-week abstinence period showed high oral ethanol self-administration during adulthood compared to rats that began consumption as adults (PND: 92-125). Moreover, alcohol-preferring male rats exposed to 15% ethanol in adolescence (PND: 30-60) exhibited accelerated acquisition of oral self-administration in adulthood (PND: 75) and a high breakpoint level in comparison to saccharine-exposed rats. These findings suggest that ethanol exposure during adolescence increased the rats’ susceptibility to the reinforcing effects of ethanol in later stages of life (Amodeo et al., 2017, Toalston et al., 2015).

Sex is another factor associated with ethanol intake; for instance, adult female rats consumed more sweetened ethanol than adult males when they were given access to ethanol (6% EtOH + 0.1% saccharin) for four days, two hours per day, followed by access to a higher concentration of ethanol (10% EtOH + 0.1% saccharin) for another four days (Vetter-O’Hagen et al., 2009), or when given continuous access to 10% ethanol for 21 days (Priddy et al., 2017). However, access to alcohol every other day for six weeks in a two-bottle-choice paradigm revealed no sex or age differences in ethanol consumption (Schramm-Sapyta et al., 2014). In addition to age and sex, some studies have revealed that sugar exposure could lead to alcohol intake. In male adult rats, for example, intermittent 12-hour access to a 10% sugar solution over 21 days induced a higher intake of 9% unsweetened ethanol (4 days/ 20 days) after the sugar treatment compared to rats that never consumed sugar or rats with previous ad-libitum sugar access (Avena et al., 2004).

Furthermore, continuous sugar access for a month, followed by a semi-forced alcohol exposure paradigm (i.e., ad libitum access to alcohol instead of water), induced alcohol preference in young adult male rats. This suggests that long-term sucrose consumption during a period of sexual maturation could predispose rats to prefer alcohol as adults (Dorofeikova et al., 2017). However, the study did not report any metabolic outcome of prolonged sugar consumption before alcohol exposure, nor did it specify the period of that exposure.

Furthermore, excessive consumption of sweets, such as sugar, leads to a robust appetitive memory that involves the activity of several reward-related brain areas. (Caynas-Rojas et al., 2019, Miranda et al., 2017). In this regard, a study showed that ad libitum exposure to sucrose for 14 days delays the acquisition of conditioned taste aversion and leads to escalating consumption due to the inability to learn new negative consequences associated with the taste of sugar (Vera-Rivera et al., 2020).

Despite this evidence, the influence of sugar consumption on alcohol preference and intake remains inconclusive, particularly considering factors such as age, sex, and the pattern of sugar access. Since drinking sugary alcohol solutions is common, particularly in adolescence, the present work examines the effect of long-term and ad libitum sugar exposure on acute preference and net intake of sugary alcohol. Furthermore, this work explores the implications of sex, age, and scheme of access to sugar between preference tests, as well as the transition from adolescence to adulthood.

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