Pilot Project Program
Yale-SCOR Pilot Project Program supports promising new research that has the potential to advance women's health and tobacco use by demonstrating direct practical benefit for the treatment of female smokers and the generation of feasibility data for external funding applications.
Pilot Project support will be awarded for studies related to the development of gender-sensitive treatments for smoking especially those that advance women's health regarding tobacco use, represent a new direction in sex- and gender-difference research in tobacco use, and use an interdisciplinary perspective.
Funded Pilot Projects:
Our funded pilot projects which add to the synergy of our center and increase our T1-T4 translation.
- "Gender differences in dynamic dopamine images: A new view of the neurochemistry of smoking"
As one example, we funded Dr. Evan Morris and Kelly Cosgrove to develop a technology to examine real time dopamine release in response to in-vivo smoking. With pilot funds, they developed a new PET technology and demonstrated that men and women have distinct real-time dopamine signatures in response to in-vivo smoking (Fig 1). Men respond consistently and rapidly in the ventral striatum, whereas women respond faster in a discrete subregion of the dorsal putamen. This finding, that men activate more ventrally than women, is consistent with our working hypothesis that men smoke more for the positive reinforcing effects of cigarettes, whereas women smoke more for other reasons, such as mood regulation. These findings have been translated to 2 funded grants to develop this innovative technology further (R21DA032791) and to use it as a tool to study sex differences in medication response (R01DA038709). This progress demonstrates our ability to identify and support high risk/high reward projects involving technology development, tracer development, and collaboration with industry to gain access to novel targets.
Cosgrove, KP, Wang, S, Kim, S-J, McGovern, E, Nabulsi, N, Gao, H, Labaree, D, Tagare, H, Sullivan, J, and Morris, ED (2014). Sex-Differences in the Brain's Dopamine Signature of Cigarette Smoking. Journal of Neuroscience,34(50):16851-5. PubMed PMID:25505336; PubMed Central PMCID: PMC4261105. http://www.ncbi.nlm.nih.gov/pubmed/25505336
- "Sex-dependent regulation of synaptic transmission in the prefrontal cortex by chronic exposure to guanfacine"
- “Dissecting the molecular and cellular substrates of guanfacine-induced mood regulation”
- "Does CERC-501 Attenuate Stress-precipitated Smoking Lapse?” CERC 501 (previously known as LY2456302) is a small molecule, high-affinity, selective kappa opioid receptor (KOR) antagonist.
- “Sex-specific investigations of metyrapone and oxazepam effects on mood regulation." EMB-001, a combination of the cortisol inhibitor, metyrapone, and the benzodiazepine, oxazepam, has been proposed as a novel therapeutic agent for treating substance abuse. The project evaluate whether EMB-001 has antidepressant-like effects in a hypercholinergic model of depression-like behaviors.
- "Developing PET imaging agent for in vivo imaging of 11α-hydroxysteroid dehydrogenase type 1 (11α-HSD1) in humans.” 11α-HSD1 is a reductase that converts cortisone to the active hormone cortisol and thus a key element in regulation of HPA axis and glucocorticoid homeostasis. As a key regulator of cortisol, 11α -HSD1 is an important target for investigation of the pathophysiology in stress-related disorders, including addiction, potentially leading to the development of novel therapeutic agents.