Research report Opiate-like effects of sugar on gene expression in reward areas of the rat brain

Drugs abused by humans are thought to activate areas in the ventral striatum of the brain that engage the organism in important adaptive behaviors, such as eating. In support of this, we report here that striatal regions of sugar-dependent rats show alterations in dopamine and opioid mRNA levels similar to morphine-dependent rats. Specifically, after a chronic schedule of intermittent bingeing on a sucrose solution, mRNA levels fortheD2dopaminereceptor,andthepreproenkephalin andpreprotachykiningenesweredecreased indopamine-receptive regions ofthe forebrain, while D3 dopamine receptor mRNA was increased. While morphine affects gene expression across the entire dopamine-receptive striatum, significant differences were detected in the effects of sugar on the nucleus accumbens and adjacent caudate-putamen. The effects of sugar on mRNA levels were of greater magnitude in the nucleus accumbens than in the caudate-putamen. These areas also showed clear differencesin the interactions among the genes, especially between D3R and the othergenes. This was revealed by a novelmultivariate analysis method that identified cooperative interactions among genes, specifically in the nucleus accumbens but not the caudate-putamen. Finally, a role for these cooperative interactions in a load-sharing response to perturbations caused by sugar was supported by the finding of a different pattern of correlations between the genes in the two striatal regions. These findings support a major role for the nucleus accumbens in mediating the effectsofnaturallyrewardingsubstancesandextendananimalmodelforstudyingthecommonsubstratesofdrugaddictionandeatingdisorders.