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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA014159-03
Application #
6807067
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2002-01-29
Project End
2005-01-28
Budget Start
2004-01-29
Budget End
2005-01-28
Support Year
3
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Pecoraro, Norman; Gomez, Francisca; Dallman, Mary F (2005) Glucocorticoids dose-dependently remodel energy stores and amplify incentive relativity effects. Psychoneuroendocrinology 30:815-25
Pecoraro, Norman; Dallman, Mary F (2005) c-Fos after incentive shifts: expectancy, incredulity, and recovery. Behav Neurosci 119:366-87
Pecoraro, Norman; Gomez, Francisca; la Fleur, Susanne et al. (2005) Single, but not multiple pairings of sucrose and corticosterone enhance memory for sucrose drinking and amplify remote reward relativity effects. Neurobiol Learn Mem 83:188-95
Pecoraro, Norman; Reyes, Faith; Gomez, Francisca et al. (2004) Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology 145:3754-62
Dallman, Mary F; Pecoraro, Norman; Akana, Susan F et al. (2003) Chronic stress and obesity: a new view of ""comfort food"". Proc Natl Acad Sci U S A 100:11696-701