Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction

BackgroundFood restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed.MethodsAnalysis of gene expression profiles in male C57BL/6J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a 5-day food restriction. Quantitative polymerase chain reaction was used to validate these findings and determine the time course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by enzyme-linked immunosorbent assay. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals.ResultsBrief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to nonrestricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state.ConclusionsThese data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress.