Starvation Strengthens Addiction

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Science Translational Medicine  28 Aug 2013:
Vol. 5, Issue 200, pp. 200ec142
DOI: 10.1126/scitranslmed.3007309

In the United States alone, more than 20 million people suffer from eating disorders (anorexia nervosa, bulimia, or binge eating), which have the highest mortality rate among psychiatric conditions and are associated with destructive behaviors. One such behavior is drug and alcohol abuse, which occurs in 50% of people with eating disorders compared with 9% of the general population. Now, Branch and colleagues identify alterations in the brain that may serve as new therapeutic targets for some of these behaviors.

It is well known from rodent studies that food restriction increases self-administration of most major classes of abused drugs. Because feeding and abused drugs increase concentrations of extracellular dopamine in specific areas of the brain, Branch et al. hypothesized that dopaminergic circuits might play a role in starvation-induced addiction. The authors focused their study on dopamine-containing neurons in the substantia nigra of laboratory mice and found that the firing rate of these cells increased after food restriction. In contrast to animals fed ad libitum, firing increased further when the psychomotor stimulant cocaine was given to food-restricted mice. The boost in firing of dopamine-containing neurons likely resulted from enhanced responses of these cells to glutamate-mediated stimulation. The authors concluded that food restriction increases the responsiveness of dopamine-containing neurons to cocaine, enhancing the effects of cocaine on the brain.

The new work suggests that food restriction amplifies the addictive effects of cocaine via mechanisms that involve glutamate-mediated stimulation of dopamine-containing neurons in the substantia nigra, an area of the brain involved in reward, addiction, and motor behavior. If similar mechanisms also operate in patients, these findings have the potential to facilitate the development of specific interventions for addiction in people with eating disorders.

S. Y. Branch et al., Food restriction increases glutamate receptor-mediated burst firing of dopamine neurons. J. Neurosci. 33, 13861–13872 (2013). [Full Text]

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