? Basic and clinical research indicate a close association between ingestive behavior and drug-seeking. This laboratory has shown that sustained negative energy balance augments behavioral and cellular effects of psychostimulants. A key endocrine response to negative energy balance is hypoinsulinemia, evident in both plasma and cerebrospinal fluid (CSF). The objective of this proposal is to determine whether central insulin replacement, as delivered by osmotic minipumps, prevents the augmentation of amphetamine effects in chronically food-restricted rats.
The first aim i s to determine if the output of the minipump remains stable throughout a 14-day period, and whether addition of an anti-aggregant or protease inhibitor helps to maintain delivery of the intended dose.
The second aim i s to determine the dose of insulin that restores CSF insulin level of food-restricted rats to the control level, as measured by CSF sampling and radioimmunoassay. The third and fourth aims are to determine if intracerebroventricular insulin replacement during food restriction reverses the augmentation of amphetamine's stimulant and rewarding effects. Stimulant effects are measured using photobeam interruption to count horizontal and vertical movements. Rewarding effects are measured by the degree of threshold-lowering for electrical brain stimulation reward. Results of this research may shed light on the high comorbidity of drug abuse and eating disorders. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA016158-03
Application #
6797957
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2002-09-20
Project End
2005-09-19
Budget Start
2004-09-20
Budget End
2005-09-19
Support Year
3
Fiscal Year
2004
Total Cost
$39,678
Indirect Cost
Name
New York University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016