Behavior-based discovery of small-molecule modulators of neurochemical signaling pathways that underlie addiction
Active Project Grant Awarded Last action
- Award ID
- R01DA056358
- Recipient
-
New York University UEI M5SZJ6VHUHN8 Part of New York University
- Awarding agency
-
National Institute on Drug Abuse
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,840,326
Award facts
- Assistance listing
- 93.279 Drug Use and Addiction Research Programs
- Completion date 88% complete
- Place of performance
- New York, NY 10016, USA
Award details come from USAspending.gov.
Description
- Abstract
- Addiction is a complex pathology of neural circuits that function in reward-processing, impulse control, and goal-directed behaviors. Small molecules targeting neuromodulator signaling pathways that function in these circuits are important therapeutics for the treatment of addiction. There is an urgent need to improve the pharmacology used to treat addiction. To address this need, we have developed methods that uses behavior- based screens to interrogate a novel source of natural products for effects on neuromodulator signaling in the nervous system of a microscopic animal - the nematode c. Elegans. The natural products that we will screen are microbial metabolites that have eluded detection because they are not expressed under basal conditions but can only be elicited by environmental triggers. This microbial 'dark metabolome' contains small molecules with a wide variety of biological activities. These compounds have not yet been assayed for effects on the animal nervous system, and they constitute a rich and untapped resource for novel psychopharmacology. Through screens designed to demonstrate proof-of-concept, we have already identified compounds that strongly and specifically act on a circuit that uses neuropeptides and serotonin to generate behavior. We have also designed behavior-based screens for novel modulators of dopamine signaling. In addition to providing the opportunity to perform high-throughput behavior-based screens, the powerful genetics of the c. Elegans model allows assignment of neuroactive compounds to specific neuromodulator signaling pathways. Successful completion of the aims of this project will generate enhanced and expanded libraries of novel natural products never before assayed for effects on the nervous system, identify novel small-molecule regulators of neural circuits, and match those compounds to specific neuromodulator signaling systems integral to the pathology of addiction.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $567,245 | |
| Amendment | $581,283 | |
| Amendment | $594,869 | |
| Amendment | $594,869 | |
| Amendment | $604,962 | |
| Amendment | $604,962 | |
| Amendment | $646,068 | |
| Original award | $646,068 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Ohio State University | $185,645 | |
| The Trustees Of Princeton University | $554,799 | |
| The Trustees Of Princeton University | $568,530 | |
| Ohio State University | $190,239 | |
| Ohio State University | $203,024 | |
| The Trustees Of Princeton University | $202,823 |
Quick answers
Who received award R01DA056358?
R01DA056358 was awarded to New York University by National Institute on Drug Abuse (National Institutes of Health) on July 15, 2022.
How much is award R01DA056358 worth?
$4,840,326 has been obligated on R01DA056358.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award