Homeostatic Substrates of Incentive Re-Valuation

University Of California San Francisco, San Francisco CA

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Abstract

Drugs of abuse are supernormal rewards that interact strongly with regulated homeostatic variables, such as hunger and stress, using similar physiological substrates, and become "abused" by devaluing normal incentives. These studies will characterize neural-hormonal systems determining the expression of incentive relativity effects for sucrose, to show how homeostatic variables normally operate to re-instate the value of typical incentives following exposure to a "supernormal" reward, and suggest how they may operate (or fail to operate) during drug abuse. Rats will be trained to devalue a 4% sucrose solution by giving them prior experience with a 32% solution, demonstrated by suppressed intake of the normally rewarding 4% solution relative to controls drinking 4% only. Relativity effects will be exacerbated in a second set of animals by food deprivation. Radioimmunoassays and telemetry will determine whether 32% sucrose solutions entrain circadian feeding rhythms relevant to drugs (corticosterone, insulin, leptin, body temperature, activity), and how major energetic hormone profiles change as reward value for the 4% solution is gradually re-instated over days. C-fos immuno-histo-chemistry will identify brain regions activated by incentive relativity effects, and those activated during recovery from incentive relativity effects. In situ hybridization will be used to identify mRNAs for food-regulatory peptides implicated in drug use (neuropeptide Y, corticotropin-releasing factor, cocaine-amphetamine- regulated transcript) in specific brain circuits. The final pre-shift day (32%) will be compared to Days 1, 2, 4, and 8 of the post-shift (4%), by which time recovery should be complete.