Neural systems that evolved to motivate and reinforce foraging and food intake also underlie drug-seeking and self-administration. The fact that some of these drugs can cause addiction raises the logical possibility that some foods might also cause addcition. Many people claim that they feel compelled to eat sweet foods, similar in some ways to how an alcoholic might feel compelled to drink. Therefore, we developed an animal model to investigate why some people have difficulty moderating their intake of palatable foods, such as sweet beverages.
In this animal model, rats are food deprived daily for 12 h, then after a delay of 4 h into their normal circadian-driven active period, they are given 12-h access to a sugar solution and chow. As a result, they learn to drink the sugar solution copiously, especially when it first becomes available each day.
After a month on this intermittent-feeding schedule, the animals show a series of behaviors similar to the effects of drugs of abuse. These are categorized as “bingeing”, meaning unusually large bouts of intake, opiate-like “withdrawal” indicated by signs of anxiety and behavioral depression (Colantuoni et al., 2001
), and “craving” measured during sugar abstinence as enhanced responding for sugar (Avena et al., 2005
). There are also signs of both locomotor and consummatory “cross-sensitization” from sugar to drugs of abuse (Avena et al., 2004
, Avena and Hoebel, 2003b
). Having found these behaviors that are common to drug dependency with supporting evidence from other laboratories (Gosnell, 2005
, Grimm et al., 2005
, Wideman et al., 2005
), the next question is why this happens.
A well-known characteristic of addictive drugs is their ability to cause repeated, intermittent increases in extracellular dopamine (DA) in the nucleus accumbens (NAc) (Di Chiara and Imperato, 1988
, Hernandez and Hoebel, 1988
, Wise et al., 1995
). We find that rats with intermittent access to sugar will drink in a binge-like manner that releases DA in the NAc each time, like the classic effect of most substances of abuse (Avena et al., 2006
, Rada et al., 2005b
). This consequently leads to changes in the expression or availability of DA receptors (Colantuoni et al., 2001
, Spangler et al., 2004
Intermittent sugar access also acts by way of opioids in the brain. There are changes in opioid systems such as decreased enkephalin mRNA expression in the accumbens (Spangler et al., 2004
). Signs of withdrawal seem to be largely due to the opioid modifications since withdrawal can be obtained with the opioid antagonist naloxone. Food deprivation is also sufficient to precipitate opiate-like withdrawal signs (Avena, Bocarsly, Rada, Kim and Hoebel, unpublished, Colantuoni et al., 2002
). This withdrawal state involves at least two neurochemical manifestations. First is a decrease in extracellular DA in the accumbens, and second is the release of acetylcholine (ACh) from accumbens interneurons. These neurochemical adaptations in response to intermittent sugar intake mimic the effects of opiates.
The theory is formulated that intermittent, excessive intake of sugar can have dopaminergic, cholinergic and opioid effects that are similar to psychostimulants and opiates, albeit smaller in magnitude. The overall effect of these neurochemical adaptations is mild, but well-defined, dependency (Hoebel et al., 1999
, Leibowitz and Hoebel, 2004
, Rada et al., 2005a
). This review compiles studies from our laboratory and integrates related results obtained by others using animal models, clinical accounts and brain imaging to answer the question: can sugar, in some conditions, be “addictive”?