Glucocorticoids dose-dependently remodel energy stores and amplify incentive relativity effects.

To test whether glucocorticoids amplify incentive motivation, three groups of rats were adrenalectomized and replaced subcutaneously with pellets of corticosterone (B), containing 0, 30, or 80% B and cholesterol. A fourth group of sham adrenalectomized rats received cholesterol pellets. Animals were placed on a four-arm maze baited with 32% sucrose for 5-min daily sessions. After 7 days of minimal drinking on the maze at free-feeding weights, their body weights were gradually reduced to 90% of their free-feeding weights for the next 12 days (pre-shift phase). The sucrose concentration was reduced to 4% for the next 2 days (post-shift phase). B dose-dependently increased 32% sucrose intake, insulin secretion, and relative fat depots. Intake was reduced similarly in all groups following the shift to 4%, resulting in a relative B-dependent intake suppression following the shift to 4%. Videoscoring of locomotor activity indicated that search behaviors were not different between groups prior to the shift to 4%, whereas the increase in search behavior following the shift to 4% sucrose was entirely B-dependent. These data were predicted by a new model of chronic stress positing two regulatory axes on brain by glucocorticoids: one indirect axis by which glucocorticoids remodel energy stores to provide metabolic feedback and a direct axis whereby glucocorticoids act directly on brain to remodel appetitive structure.