As a consequence of Super-storm Sandy and its aftermath, two significant losses set back progress on our multi-PI project, 1 R01 DA033811, Diet, Insulin, Dopamine, and Reward, PIs: Margaret Rice (contact), Kenneth Carr, and Maarten Reith. The first was lost time, and the second was loss of a transgenic mouse line, in which acetylcholine (ACh) was genetically deleted (as described in Patel et al., Nat. Commun., 2012). We are requesting a with-cost extension of 4 months, and a supplement to re-establish this key mouse line. Our laboratories are all fully functional, and we have current IACUC approval for all experiments in this project: Rice protocol 120313-02, approved 4/9/13;Carr protocol 120604-02, approved 2/1/2013;Reith protocol 120807-01, approved 8/30/2012. As also noted in our recently submitted Progress Report, the unobligated balance on this project was 36% of the total budget as of 5/31/13 ($187,879 of the total award, which was $525,864, direct + indirect). It should be noted that 30% carry-over was necessarily expected because Year 1 was truncated by 30% (to 8.5 mo. 9/15/2012 - 5/31/2013). The small additional balance (6%) reflected some decrease in supply expenditures because of down-time in Sandy (although salary support necessarily continued), as well as conservative spending to buffer future budget years in which expenses are expected to increase, and the annual award amount to remain flat or even decrease, as occurred in the current budget year (Year 2). Thus, the current unobligated balance is absolutely essential to achieve the goals of the original application. The present request for a with-cost extension and supplement is a completely separate issue that addresses compensation to restore losses of time and resources from Sandy.
Eating disorders and substance abuse are significant health risks. The pathology of both involves brain reward circuitry; but whether the same pathways are affected is unclear; in part because of segregation of research on diet vs. drugs. This multi-PI; multi-disciplinary project is built around our preliminary evidence that insulin; a recognized regulator of satiety and metabolism; is also a reward signal in the brain. This project has the potential to change the way that insulin is viewed; and thereby lead to novel crossover therapies to treat both obesity and addiction.
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|Sulzer, David; Cragg, Stephanie J; Rice, Margaret E (2016) Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia 6:123-148|
|Carr, Kenneth D (2016) Nucleus Accumbens AMPA Receptor Trafficking Upregulated by Food Restriction: An Unintended Target for Drugs of Abuse and Forbidden Foods. Curr Opin Behav Sci 9:32-39|
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