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 for the D2 dopamine receptor, and the preproenkephalin and preprotachykinin genes were decreased in dopamine-receptive regions of the 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 differences in the interactions among the genes, especially between D3R and the other genes. This was revealed by a novel multivariate 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 effects of naturally rewarding substances and extend an animal model for studying the common substrates of drug addiction and eating disorders.
Spangler
Rudolph
R
Laboratory of Behavioral Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. rudolph.spangle@rockefeller.edu
Wittkowski
Knut M
KM
Goddard
Noel L
NL
Avena
Nicole M
NM
Hoebel
Bartley G
BG
Leibowitz
Sarah F
SF
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D001068:Feeding and Eating Disorders / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3; D012201:Reward; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology*; D015320:Tachykinins / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
C493595:Drd3 protein, rat; D004745:Enkephalins; D018847:Opioid Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015320:Tachykinins; C044206:preprotachykinin; D013395:Sucrose; D009020:Morphine; C033660:preproenkephalin