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Two groups of rats, one bearing bilateral excitotoxic lesions of the medial prefrontal cortex (mPFC) and one sham-lesioned group, were run in a successive negative contrast paradigm. Both groups had telemeters implanted to monitor core temperature and activity. After ad libitum baseline and food restriction to 85% body weights, rats received a sucrose solution once daily for 5 min and 30 s at 10:30 h. They received their preshift 32% sucrose solution for 14 days followed by a sucrose concentration reduction (downshift) to 4% sucrose for 12 days. Rats were then upshifted to 32% for six additional days before being downshifted to 4% for the next 6 days. There were no differences in intake of the 32% sucrose during the preshift. All rats showed profound suppression of intake upon the shift to 4% sucrose. On the first day of the unexpected 4% sucrose, lesioned rats showed an enhanced psychogenic fever compared with Shams, whereas on the second day of 4% sucrose they showed an impaired ability to blunt that fever compared with Shams. In addition, lesioned rats showed greater rates of recovery and asymptotic drinking of the subsequent 4% sucrose solution than Shams, indicating impairments in the encoding or retrieval of the shift. In addition, lesioned rats showed enhanced entrainment to the 32% sucrose meals, normal damping of anticipation, and enhanced spontaneous recovery of anticipatory thermal responses to the calorically impoverished 4% solutions. These failures to inhibit responding point to a failure in interference learning in rats bearing lesions of the mPFC.

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.

Scheduled daily injections of methamphetamine (MA) produced locomotor activity that preceded and followed the usual time of injection in rats housed under conditions of constant, moderately dim light and temporally distributed feeding. A circadian basis for pre-injection time activity was supported by its anticipatory timing in the apparent absence of reliable preceding external cues and by its persistence on a test day on which the rats remained undisturbed. Post-injection time locomotor activity also persisted on the test day, occurring from 24 to 29 h after the final MA injection. These results indicate that MA injections engage circadian processes underlying locomotor activity, and they raise the possibility that intake of drugs of abuse by humans may facilitate drug taking or relapse at times of day related to previous drug use.