1 Bowles Center for Alcohol Studies, CB# 7178; Thurston-Bowles Building, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178 and
2 Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7175, USA
Received 2 November 1998; accepted 29 December 1998
ABSTRACT
This report reviews a series of studies demonstrating a relationship between the consumption of sweets and alcohol consumption. There is consistent evidence linking the consumption of sweets to alcohol intake in both animals and humans, and there are indications that this relationship may be at least partially genetic in nature. Alcohol-preferring rats have a tendency to consume sucrose and saccharin solutions far beyond the limits of their normal fluid intake and this has been proposed to be a model of the clinical phenomenon known as loss of control. Furthermore, rats and mice, genetically bred to prefer alcohol, tend to choose more concentrated sweet solutions, compared to animals which do not prefer alcohol. Similar tendencies to prefer ultra-sweet solutions have been noted in studies of alcoholic subjects, with most alcoholics preferring sweeter sucrose solutions than do controls. Evidence also exists that those alcoholics who prefer sweeter solutions may represent a familial form of alcoholism. Finally, consumption of sweets and/or sweet solutions may significantly suppress alcohol intake in both animals and in alcoholics. Carbohydrate structure and sweet taste may contribute to this effect through different physiological mechanisms involving serotonergic, opioid, and dopaminergic functions. The possibility that there is concordance between sweet liking and alcohol consumption and/or alcoholism has theoretical, biological, and diagnostic/practical implications.
INTRODUCTION
The search for phenotypic markers of risk for alcoholism has led to the identification of several promising biological variables [e.g. a reduced behavioural response to alcohol (Schuckit and Gold, 1988), a reduced P300 evoked potential (Begleiter et al., 1987
), and lowered activity of the enzyme monoamine oxidase type B (MAOB) in platelets (Devor et al., 1994
) etc.] that may be associated with a higher risk for developing this disease. However, despite the existence of intensive investigation in this field, health professionals still do not have a test that can gauge the risk of developing alcoholism, indicating that further research in this area is needed. In the present review, we shall examine accumulated evidence for an association between consumption of sweet substances and excessive alcohol intake in both animals and humans.
CORRELATION BETWEEN CONSUMPTION OF SWEETS AND ALCOHOL
The first evidence connecting the consumption of sweets with alcohol intake came from animal studies. Ramirez and Sprott (1978) and Forgie et al. (1988) reported that C57BL mice, known for their high voluntary alcohol intake, consume much larger quantities of saccharin solution than do DBA/2J mice, known for their relatively low alcohol intake (McClearn and Rodgers, 1959). However, the first direct association between consumption of saccharin solution and subsequent alcohol intake (r = 0.33) was shown in an experiment with randomly bred albino rats (Kampov-Polevoy et al., 1990
). Later, a similar association was demonstrated in Wistar rats (Kampov-Polevoy et al., 1994
). In the latter study, the correlation between voluntary consumption of a 0.1% saccharin solution and subsequent voluntary consumption of 15% alcohol solution, offered along with a free choice of water, was high (r = 0.7). Similar findings regarding the association between consumption of saccharin solution and alcohol in Wistar rats were also reported by other research groups (Gosnell and Krahn, 1992
; Bell et al., 1994
; Gahtan et al., 1996
; Koros et al., 1998
).
An association between saccharin consumption and subsequent alcohol intake can be seen more clearly in animal strains/lines genetically developed for alcohol preference or alcohol avoidance. In 1992, we reported that alcohol-preferring P rats drink almost twice as much 0.1% saccharin solution as alcohol-avoiding NP rats (Sinclair et al., 1992). A greater difference was found between alcohol-preferring AA rats, which drank 77.5 ± 12.6 ml/kg/day of 0.1% saccharin solution, offered in a free choice with water, compared to alcohol-avoiding ANA rats, which drank 2.1 ± 0.6 ml/kg/day of the above solution. Similar baseline water intake occurred in both lines (Sinclair et al., 1992
). Overstreet et al. (1993) measured saccharin and alcohol intake in seven rat strains/lines known to differ in their preference for ethanol. Of these, Fawn Hooded (FH), alcohol-preferring (P) and Maudsley Reactive (MR) rats are known to voluntarily consume large quantities of ethanol and the alcohol-non-preferring (NP), Maudsley Non-reactive (MNRA), Flinders Sensitive (FSL) and Flinders Resistant (FRL) lines of rats are known to avoid ethanol. Saccharin and alcohol intake were highly correlated (r = 0.61; P < 0.001) across all strains. When studied in the genetically heterogeneous F2 progeny derived from cross-breeding of the ethanol-preferring FH rats with the ethanol-non-preferring FRL rats, the correlation between saccharin and alcohol intake remained high (r = 0.65; P < 0.001), suggesting a genetically determined link between these two variables. Later, Stewart et al. (1994) demonstrated that alcohol-preferring P rats consume greater amounts of sucrose solution compared with alcohol-non-preferring NP rats, and showed a positive correlation between saccharin and alcohol intakes in F2 progeny from cross-breeding of the P and NP rats (Stewart et al., 1997
).
A high genetic correlation (r = +0.77) between saccharin and alcohol intake has also been reported in 15 inbred mouse strains (Belknap et al., 1993). A similar correlation between sucrose consumption and alcohol intake can be seen in the F2 generation of crosses between alcohol-preferring C57BL/ 6ByJ and alcohol-avoiding 129/J strains of mice (Bachmanov et al., 1996
). Further analysis by the latter authors showed that intakes of sucrose and ethanol are influenced by a few genes and that the genetically determined component of these correlations was stronger than the component related to environmental factors'. However, in contrast, several genetic studies in mice have so far failed to report overlapping genetic control over the consumption of sweets and the consumption of alcohol (Phillips et al., 1994
; Melo et al., 1996
; Bachmanov et al., 1997
).
There is also evidence indicating that a line of rats selectively bred for high 5HT1A receptor sensitivity drinks more saccharin, but not more alcohol than its control line (Overstreet et al., 1996). Furthermore, rats that have been selectively bred for differences in saccharin intake do not drink differential amounts of alcohol (Badia-Elder et al., 1994
). At this time, we are unable to explain these discrepancies. It is possible that the transformation of a predisposition for excessive alcohol intake, indicated by sweet liking, into actual alcohol consumption is possible only under certain conditions, such as initiation by forced alcohol exposure (Kampov-Polevoy et al., 1995a
), exposure to sweetened alcohol (Kampov-Polevoy et al., 1994
), or the presence of certain personality traits, as has been shown in human experiments (Kampov-Polevoy et al., 1998a; see also the discussion below). It is also possible that, if consumption of alcohol is associated in animals with some aversive effects (e.g. high taste aversion, accumulation of acetaldehyde, etc.), then transformation of a predisposition for alcohol intake, as indicated by sweet liking, into actual alcohol consumption, is unlikely.
In summary, a variety of studies performed in at least seven strains/lines of rats and 15 inbred strains of mice indicate a close association between consumption of sweet solutions (i.e. saccharin, sucrose) and subsequent alcohol intake in a free-choice situation. This association has not been found in two co-developed rat strains, indicating certain limitations to the predictive value of sweet consumption regarding subsequent alcohol intake. This association appears to be at least partially under genetic control, and there are indications that the genetic component of this association is stronger than the component related to environmental factors. However, the specific genes controlling consumption of both alcohol and sweet substances have not been identified.
Although the mechanism of association between consumption of sweet solutions and alcohol intake is not fully understood, it may be speculated that it is determined by a common mechanism mediating the rewarding properties of both sweet solutions and ethanol. For example, the brain opioid system is known in part to mediate the hedonic response to alcohol (for review, see Froehlich and Li, 1994) and this system may be involved in mediation of the rewarding effect of sweet solutions and also of sweets in general. Sweets have been shown to stimulate the endogenous opioid system both by inducing a release of ß-endorphin (Dum et al., 1983; Dum and Herz, 1984
; Gianoulakis et al., 1990
) and by increasing the binding affinity of opioids at receptor sites (Marks-Kaufman et al., 1988
). It has also been shown that various drugs of abuse and palatable foods share the ability to increase the extracellular concentration of dopamine in the nucleus accumbens (for discussion, see Di Chiara et al., 1998), suggesting that alcohol and sweets may share common dopaminergic mechanisms in mediating their hedonic effects.
SACCHARIN-INDUCED POLYDIPSIA
One of the interesting characteristics of the saccharin intake of alcohol-preferring rats is their tendency to consume saccharin beyond the limit of normal daily fluid intake (DFI). This tendency was initially reported in randomly bred rats (Kampov-Polevoy et al., 1990). In this study, it was noted that, although all the rats studied had a high preference for 0.1% saccharin solution when offered a free choice of saccharin and water, some of them (40%) consumed saccharin solution on average 32% over the limit of their normal DFI, a condition we described as saccharin-induced polydipsia. Subsequently, these polydipsic rats consumed almost 10 times as much alcohol during the first week of an alcohol/water choice experiment as rats that consumed saccharin solution within the limits of their normal DFI.
These findings have been replicated in a study (Kampov-Polevoy et al., 1994) which demonstrated that, given a free choice between water and 0.1% saccharin solution, 29% of male Wistar rats demonstrated an average 34% DFI increase above baseline (they were defined as DFI Increasers), while the rest of Wistar rats consumed saccharin solution within the limits of their normal DFI (they were defined as DFI Non-increasers). The DFI Increasers began to consume 15% alcohol solution in a free-choice situation practically from their first contact, gradually increasing their consumption over the time of the experiment. Exposure of DFI Increasers to sweetened alcohol solution resulted in a significant increase in their alcohol consumption, which remained elevated for at least 4 days after these rats were returned to unsweetened alcohol. DFI Non-increasers, however, began to consume alcohol later (only after 5 days of contact with it) and consumed practically the same amount of alcohol throughout the first 24 days of ethanol/water choice. Furthermore, exposure to sweetened alcohol solution did not significantly affect the alcohol intake of DFI Non-increasers.
Rats genetically selected for alcohol preference show an even-greater saccharin-induced polydipsia. For example, high-alcohol drinking (HAD) rats exhibited a 370% increase in daily fluid intake when 0.1% saccharin solution was available along with water, whereas low-alcohol drinking (LAD) animals consumed saccharin within their normal DFI (Overstreet et al., 1997). Saccharin-induced polydipsia was shown to be a reliable predictor of subsequent alcohol intake, with a correlation coefficient (r) between these two variables in P rats of up to 0.9 (Kampov-Polevoy et al., 1995a
). When a factor analysis was performed using 13 different behavioural variables in four alcohol-preferring (AA, HAD, FH, and P) and five alcohol-non-preferring (ACI, ANA, FRL, LAD, and NP) rat lines/strains, saccharin intake and especially saccharin-induced polydipsia were shown to have the strongest associations with different parameters of alcohol intake (e.g. intake as such, alcohol preference, alcohol acceptance), compared to other behavioural tests (Overstreet et al., 1997
). This conclusion is also in agreement with a recent report indicating that saccharin-induced polydipsia is a better predictor of subsequent alcohol intake than are behavioural parameters measured in an open-field situation (Koros et al., 1998
).
The dramatic increase in DFI in the presence of saccharin exhibited by alcohol-preferring rats may be an animal analogue of the clinical phenomenon known as loss of control'. In the clinical situation, loss of control refers to the behaviour in which a rewarding substance is taken in larger amounts or over longer periods of time than is intended. Consumption of sweets may be a useful model for studying the phenomenon of loss of control in animals, especially considering the fact that the preference for a sweet taste is unlearned, and may be detected as early as several hours after birth (Maller and Turner, 1973). There also appears to be a linkage between loss of control over the consumption of sweets and the amount of subsequent alcohol intake. These findings are consistent with the human data indicating that a loss of control over food intake (including sweets) can be detected long before the development of excessive alcohol intake (Jones et al., 1985
), and that overall co-morbidity between eating disorders and substance abuse is reported to be as high as 60% (Jonas, 1990
).
Serotonin and loss of control
The brain serotonin system is known to be one of the main mechanisms involved in the process of satiation (bringing an eating episode to a halt) and in maintaining the state of satiety (the period of inhibition over further eating) (Blundell, 1984, 1987
). Initially, it was thought that this system specifically regulated the intake of carbohydrates and that serotonin deficiency was associated with carbohydrate craving (Wurtman, 1990
). Later, it was shown that the extent of the suppressive effect of serotonin on consumption of rewarding substances was proportionate to the reinforcing efficacy of these substances, regardless of their chemical structure. For example, peripherally administered serotonin decreases the intake not only of sucrose and sweet milk solutions, but also of that of a non-carbohydrate sweetener, saccharin (Montgomery and Burton, 1986
). Furthermore, the serotonin reuptake inhibitor zimelidine has been reported to have a greater effect upon consumption of 0.1% saccharin solution, as compared to a less palatable 0.025% saccharin solution or water (Gill and Amit, 1987
). It has also been shown that the brain serotonergic system regulates the intake of substances where the rewarding effect is not associated with palatability and/or caloric value, such as alcohol (for review see LeMarquand et al., 1994), morphine (Rockman et al., 1980
), amphetamine (Yu et al., 1986
), and cocaine (Peltier and Schenk, 1991
).
In recent studies, it has also been noted that serotonergic drugs had a greater effect on excessive, rather than normal consumption. For example, palatability-induced food intake appears to be more sensitive to fluoxetine treatment than deprivation-induced feeding (Leander, 1987). Similarly, long-term administration of d-fenfluramine exerts a more potent anorectic effect in rats with hyperphagia caused by dietary supplements than in control chow-fed animals (Blundell and Hill, 1989
). In another study, the selective serotonin reuptake inhibitor fluvoxamine had a greater effect, in rats, on food intake during rebound hyperphagia than on food intake during a free-feeding period (Inoue et al., 1997
). These data are consistent with our findings in rats showing that fluoxetine causes a dose-dependent reduction in excessive saccharin intake (i.e. consumption beyond the limit of normal DFI), decreasing consumption to the normal DFI level (i.e. that established when water only was available). Fluoxetine, interestingly, caused only a minimal effect on saccharin preference (Kampov-Polevoy and Rezvani, 1997
). Similarly, the alcohol suppressing effect of the serotonin 5-HT1A agonist 8-OH-DPAT can be seen only in animals with a high level of alcohol preference, with no change in alcohol intake having been reported in a low-preference group (Svensson et al., 1989
).
Therefore, there is evidence that the brain serotonin system is involved in the regulation of consumption of rewarding substances, regardless of the mechanism of action, with elevation of the activity of the brain serotonin system causing suppression of intake of these substances. The serotonin system seems to have a stronger effect on consumption of substances with greater reinforcing efficacy, and on excessive consumption of reinforcing substances. A deficiency of the brain serotonin system may be a common mechanism underlying the development of those conditions associated with the loss of control over consumption of reinforcing substances, including eating disorders and substance abuse, and may explain the high co-morbidity rates between these disorders.
PREFERENCE FOR HIGHLY CONCENTRATED SWEET SOLUTIONS AND ALCOHOL INTAKE
Animal studies
In 1992, we reported that rats with a genetically determined predisposition to high alcohol consumption preferred more concentrated sweet solutions, compared to alcohol-avoiding rats (Sinclair et al., 1992). In this study, alcohol-preferring P and AA rats, as well as alcohol-non-preferring NP and ANA rats were tested by being given a free choice between tap water and an ascending series of saccharin concentrations, starting at 2 mg/l and doubling the concentration every day until a final level of 4096 mg/l was reached. This experiment showed that, when rats were exposed to up to the 64 mg/l saccharin solution, their preference for it was generally the same in all animal groups. However, when exposed to more concentrated saccharin solutions, alcohol-non-preferring (i.e. NP and especially ANA) rats generally had a lower preference ratio, compared to alcohol-preferring (i.e. P and AA) rats. To test the relevance of these findings to human alcoholism, we decided to evaluate the sweet preferences of alcoholics and non-alcoholic control subjects.
Human studies
Humans, like most mammals, like sweets. This preference is innate and may be detected within the first few hours after birth (Maller and Turner, 1973). However, investigation in humans has consistently revealed inter-individual variation in the degree of sweet liking, and, in fact, studies by different groups indicate that humans can generally be divided into two categories sweet-likers and sweet-dislikers. Sweet-likers report increasing pleasurable responses to increasing concentrations of sucrose across a range of 0.0 to 2.0 M. On the other hand, sweet-dislikers showed increasing pleasurable responses in the 0.00.2 M range and then showed decreasing pleasurable responses as sucrose concentrations rose above 0.3 M (Thompson et al., 1976
; Cabanac, 1979
; Looy and Weingarten, 1991
; Looy et al., 1992
). Despite differences in sweet preference, both sweet-likers and sweet-dislikers are equally able to discriminate between the strength of sucrose concentrations, suggesting that sweet preference and sweet detection are separate traits (Thompson et al., 1976
; Looy and Weingarten, 1991
). In addition, sweet-likers and sweet-dislikers retain their preferences when different sugars, such as glucose or fructose, are given (Looy et al., 1992
). Sweet preference has also been reported to be stable over time (Thompson et al., 1976
). Additionally, sweet liking does not predict preference for other primary tastes, such as salt, suggesting that the ... sweet liker/disliker distinction is a robust phenomenon which appears to generalize over, but is restricted to, sweet-tasting substances' (Looy et al., 1992
).
As an initial test of the hypothesis that sweet liking is associated with alcoholism, we compared sweet preferences in human alcoholic and non-alcoholic subjects (Kampov-Polevoy et al., 1997). The subject sample consisted of a control group of 37 Caucasian men who had never been diagnosed as alcoholics and 20 Caucasian alcoholic men who had been sober for at least 28 days during in-patient treatment. To estimate each subject's response to sucrose, five concentrations of sucrose solution (0.05, 0.10, 0.21, 0.42, and 0.83 M) were presented five times in random order for a total of 25 taste samples. For comparison, Coca Cola Classic® is a 0.33 M sugar solution. Subjects were instructed to sip the solution, to swish it around their mouths, and then to spit it out. They were then asked to rinse their mouth with distilled water, and to proceed to the next solution. To rate sweet intensity, each subject was asked to rate: How sweet was the taste?' on a 200-mm analogue scale, with one extreme labelled as Not sweet at all' and the other labelled as Extremely sweet'. Each subject was then asked to rate each solution's pleasurableness, answering the question: How much do you like the taste?', with the two poles of this analogue scale being Disliked very much' and Liked very much'.
In this experiment, both the alcoholic and the control subject groups were able to effectively discriminate between the different concentrations of sucrose. In fact, investigation of the subjects' capability to discriminate between the two weakest sucrose solutions revealed no group differences, suggesting that the alcoholics were no less sensitive in their ability to detect the sucrose taste. Compared to controls, fewer alcoholics preferred the low (0.05 and 0.1 M) sucrose concentrations (20 vs 49%; P = 0.03) and more alcoholics preferred the high (0.42 and 0.83 M) sucrose concentrations (80 vs 41%; P = 0.004). Furthermore, 65% of the alcoholics preferred the highest (0.83 M) sucrose concentration, (i.e. were sweet-likers by our definition), compared to only 16% of the control group (P = 0.0003).
Once our initial hypothesis showing that sweet liking was more prevalent in alcoholic men compared to non-alcoholic men was confirmed, we decided to test whether sweet liking is a general phenomenon among alcoholics, or whether it is associated with some particular clinical subtype thereof. Two subtype classifications that have been proposed based on clinical studies are the Type 1/ Type 2 classification of Cloninger (1987) and the Type A/Type B classification of Babor et al. (1992). The more severe forms of alcoholism (Type 2 and Type B) have been characterized by an early onset of dependence, a propensity for antisocial behaviour during alcohol intoxication, polysubstance abuse, and the high density of alcoholism in the family, reflecting a possible genetic predisposition. Furthermore, Cloninger (1987) hypothesized that Type 2 alcoholism has a personality profile consisting of high Novelty Seeking (NS), low Harm Avoidance (HA), and low Reward Dependence (RD), as ascertained from the Tridimensional Personality Questionnaire (TPQ). On the other hand, Type B alcoholics have been reported to have high NS and low RD, similar to Type 2 alcoholics yet also have a high HA (Yoshino et al., 1994).
As a next step in our study (Kampov-Polevoy et al., 1998a), we investigated if the TPQ profile of sweet-liking alcoholics fits the description of one of the two subtypes of familial alcoholism (i.e. Type 2 or Type B). The study group was an extension of the sample used in a previous study, and consisted of 52 control males, who had never been diagnosed as alcoholics, and 26 male alcoholics, who had been detoxified from alcohol for at least 28 days. The sweet-preference testing procedure was identical to that used in the previous study. In addition, all subjects completed the TPQ. It was shown that the distribution of subjects preferring different sucrose concentrations among alcoholics and controls was similar to the one described for the previous study, with 21% of controls and 62% of alcoholics preferring the highest 0.83 M sucrose concentration. The TPQ profiles of the sweet-liking alcoholics were shown to be similar to those reported by Yoshino et al. (1994) in Type B alcoholics (high NS, high HA, low RD). Further analysis indicated that the combination of preferred sucrose concentration, Novelty Seeking and Harm Avoidance, predicted alcoholic vs non-alcoholic group status at 65% sensitivity and 94% specificity, with correct classification in 85% of subjects.
Our most recent study (presented at the 9th ISBRA Congress, Kampov-Polevoy et al., 1998b) provided support for animal findings demonstrating an association between preference for stronger sweet solutions and a genetic predisposition for alcoholism (Sinclair et al., 1992). In the above human study, we evaluated the association between family history, which is known to reflect a genetic predisposition to alcoholism (Cotton, 1979; Goodwin, 1985; Schuckit, 1988; for a discussion see also Schuckit, 1991), and sweet preference, using a different sample of detoxified alcoholics (n = 32) and control non-alcoholic subjects (n = 25). Since we hypothesized that the possible link between sweet preference and a family history of alcoholism is genetic in nature, control and alcoholic groups were combined for this analysis to increase power. It was shown that 61% of individuals with a positive family history of alcoholism (FH+) preferred the strongest sucrose solution (0.83 M), compared with 19% of individuals with a negative family history of alcoholism (FH) (P = 0.001). In addition, sweet-liking FH+ alcoholics exhibited other symptoms that have been attributed to familial Type B alcoholism. Compared to other patients in this study, these subjects reported an earlier onset of heavy drinking, more alcohol consumed during drinking episodes, and more frequent episodes of antisocial behaviour during intoxication.
In summary, a growing body of evidence indicates an association between preference for stronger sweet solutions and excessive alcohol intake, both in animals (Sinclair et al., 1992) and in humans (Kampov-Polevoy et al., 1997
, 1998a
,Kampov-Polevoy et al., b
). The data regarding the TPQ personality profile, family history of alcoholism, and clinical characteristics of sweet-liking alcoholics is supportive of a hypothesis that the preference for stronger sweet solutions is associated with a familial subtype of alcoholism.
CONSUMPTION OF SWEETS SUPPRESSES ALCOHOL INTAKE
The macronutrient composition of food is known to interfere with voluntary alcohol intake both in animals and in humans (for review, see Forsander, 1998). Among the most consistent findings in this area is the observation that a high-carbohydrate/ low-protein diet suppresses voluntary alcohol intake, whereas a low-carbohydrate/high-protein diet increases it. Forsander and Sinclair (1988) reported an experiment with AA rats in which the carbohydrate/protein content of the food was systematically changed and the fat concentration was kept constant. In this experiment, voluntary alcohol consumption was found to negatively correlate with carbohydrate/protein content. Similar results were reported in mice (Mirone, 1957; Pekkanen et al., 1978
) and miniature pigs (Brown and Hutcheson, 1973
). A limited amount of human data also provides evidence that the eating of sweets may interfere with alcohol intake. In a survey of 89 538 women and 48 493 men, Colditz et al. (1991) showed a negative correlation between sucrose intake and alcohol consumption. In the book Living Sober (Alcoholics Anonymous, 1987
), which summarizes the experience of recovering alcoholics, it is emphasized that many of us even men who said that they never liked sweets have found that eating and drinking sweets allays the urge to drink'. This view is supported by Farkas and Dwyer (1984), who found that 22% of alcoholic men in their study reported that consumption of sugar and sweets helped them maintain sobriety. Another clinical report indicates that alcoholics who stay sober in treatment for more than 30 days consume significantly more sucrose than those who do not remain sober for 30 days (Yung et al., 1983
).
The suppression of alcohol consumption by a high-carbohydrate diet may be based on a serotonergic mechanism. It has been shown that carbohydrate consumption increases the plasma tryptophan/large neutral amino acids ratio in plasma (Lyons and Truswell, 1988; Møller, 1989
). This effect depends not on the sweetness of the carbohydrates, but on their insulin secretogenic properties, because of insulin's action on muscle protein catabolism, resulting in increased entry of tryptophan into the brain and a consequent enhancement of serotonin synthesis, which, in turn, suppresses alcohol intake (see earlier discussion). Another mechanism by which sugars (carbohydrates) increase brain tryptophan concentration is that of inhibition of liver tryptophan pyrrolase activity (Badawy et al., 1980
).
Non-carbohydrate artificial sweeteners have, however, also been shown to suppress voluntary alcohol intake. A 4-day exposure of naïve alcohol-preferring FH rats to 0.1% saccharin solution resulted in a 40% decrease in their subsequent alcohol intake for at least 10 consecutive days. Similar results, though of a lesser magnitude, were observed in alcohol-experienced P rats genetically selected for high alcohol intake (Kampov-Polevoy et al., 1995b).
The brain opioid system, which is known to mediate in part the hedonic response to alcohol (for review, see Froehlich and Li, 1994), may be involved in the suppression of alcohol intake by non- carbohydrate sweeteners. As mentioned earlier, sweets stimulate the endogenous opioid system, both by inducing release of ß-endorphin (Dum et al., 1983; Dum and Herz, 1984
; Gianoulakis et al., 1990
) and by increasing the binding affinity for opioids at the receptor site (Marks-Kaufman et al., 1988
). As a result of such stimulation, even a 20-min access to saccharin may substantially potentiate the hypothermic effect of morphine to a level that typically occurs in animals given large doses of morphine' (Bowers et al., 1993
). Furthermore, chronic exposure to saccharin may lead to the development of tolerance to opioids (Lieblich et al., 1983
). Such tolerance may be detected after 24 h of ingestion of sweet solutions and increases progressively over the next 5 weeks (Bergmann et al., 1985
). This tolerance may lead to a decrease in the hedonic response to alcohol, which is also mediated by the opioidergic system and, as a result, to attenuation of alcohol intake. Such a mechanism may also explain the protracted effect of saccharin consumption on subsequent alcohol intake.
From the above, it may be concluded that there is consistent evidence in the literature indicating that carbohydrate consumption may attenuate alcohol intake in both animals and humans. Although the mechanism of such action is not fully understood, it may be speculated that carbohydrate intake exerts its inhibitory effect on alcohol consumption by at least two different mechanisms. The first mechanism is an elevation in brain serotonin level, due to an increase of tryptophan transport across the bloodbrain barrier. This mechanism is taste-independent and based in part on the ability of carbohydrates to cause insulin release. The second mechanism is based on sweet taste, the hedonic response to which shares neurochemical mechanisms with the hedonic response to alcohol. This mechanism can be applied not only to carbohydrates with a sweet taste (e.g. glucose, sucrose) but also to non-carbohydrate artificial sweeteners, such as saccharin.
GENERAL CONCLUSIONS AND COMMENTS
FOOTNOTES
* Author to whom correspondence should be addressed.
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