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.
| Hao, Joy; Cabeza de Vaca, Soledad; Pan, Yan et al. (2006) Effects of central leptin infusion on the reward-potentiating effect of D-amphetamine. Brain Res 1087:123-33 |
| Cabeza de Vaca, S; Hao, J; Afroz, T et al. (2005) Feeding, body weight, and sensitivity to non-ingestive reward stimuli during and after 12-day continuous central infusions of melanocortin receptor ligands. Peptides 26:2314-21 |
| Hao, J; Cabeza de Vaca, S; Carr, K D (2004) Effects of chronic ICV leptin infusion on motor-activating effects of D-amphetamine in food-restricted and ad libitum fed rats. Physiol Behav 83:377-81 |
