Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake

Abstract

[Avena, N.M., Rada, P., Hoebel B.G., 2007. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Biobehavioral Reviews XX(X), XXX-XXX]. The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. "Food addiction" seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. "Bingeing," "withdrawal," "craving" and "cross-sensitization" are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity.

Figure 1

Meal analysis of two representative rats living in operant chambers. The one maintained on Daily Intermittent Sucrose and Chow (black lines) had an increased intake of sugar compared with one given Ad libitum Sucrose and Chow (grey lines). Hour 0 is 4 h into the dark phase. Each lever press delivers 0.1 mL of 10% sucrose. A sugar meal is defined as ending when the rat does not press for 2 min. Both rats consume several meals of about equal size on day 1 (top panel). Note that the rat with sugar available 24 h also drinks during the inactive (light) phase. By day 21 (bottom panel), the rat with sucrose and chow available for only 12 h consumes an initial “binge” of sucrose (indicated by the first arrow), followed by fewer, but larger meals, than the rat with sucrose and chow ad libitum. Sugar-bingeing rats are the ones that show signs of dependency in a battery of tests.

Figure 2

Time spent on the open arms of an elevated plus-maze. Four groups of rats were maintained on their respective diets for one month and then received naloxone (3 mg/kg, s.c.). The Daily Intermittent Glucose and Chow group spent less time on the open arms of the maze. *p<0.05 compared with the Ad libitum Chow group. From Colantuoni et al., 2002.

Figure 3

Rats that have been maintained on Daily Intermittent Sucrose and Chow are more immobile than control groups in a forced-swim test during naloxone-precipitated withdrawal. *p<0.05 compared with Ad libitum Sugar and Chow and Ad libitum Chow groups.

Figure 4

After 14 days of abstinence from sugar, rats that previously had 12-h daily access significantly increased lever pressing for glucose to 123% of pre-abstinence responding, indicating increased motivation for sugar. The group with 0.5-h daily access did not show increased responding after abstinence. **p<0.01. From Avena et al., 2004.

Figure 5

Locomotor activity in a photocell cage plotted as percent of baseline beam breaks on day 0. Rats were maintained for 21 days on the specified diets regimens. Rats maintained on Daily Intermittent Sucrose and Chow were hyperactive nine days later in response to a low dose of amphetamine, compared with control diet groups. **p<0.01. From Avena and Hoebel, 2003.

Figure 6

Intermittent sugar access alters DA receptor binding at the level of the striatum. D₁ receptor binding (top panel) increases in the NAc core and shell of animals exposed to Daily Intermittent Glucose and Chow (black bars) for 30 days compared with control animals fed chow ad libitum (white bars). D₂ receptor binding (bottom panel) decreases in the dorsal striatum in sections from taken the same animals. *p<0.05. From Colantuoni et al., 2001.

Figure 7

Rats with intermittent access to sugar release DA in response to drinking sucrose for 60 min on day 21. Dopamine, as measured by in vivo microdialysis, increases for the Daily Intermittent Sucrose and Chow rats (open circles) on days 1, 2 and 21; in contrast, DA release was attenuated on day 21 in four control groups as follows: a group that only had 1-h access to sucrose on day 1 and 21 with ad libitum chow in the interim (Sucrose Twice), Ad libitum Sucrose and Chow group, and Daily Intermittent Chow group (bottom panel). The bar on the ordinate indicates the hour (0-60 min) that sucrose or chow was available for the tests. *p<0.05. From Rada et al., 2005.

Figure 8

Extracellular DA (upper graph) decreased to 81% of baseline after naloxone injection (3 mg/kg, s.c.) in rats with a history of Daily Intermittent Sucrose and Chow. Acetylcholine (lower graph) increased to 157% in the same intermittent sugar-access rats. No effects were seen in a control group with Ad libitum Chow followed by a naloxone injection. *p<0.05, **p<0.01. From Colantuoni et al., 2002.