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Behavior-based discovery of small-molecule modulators of neurochemical signaling pathways that underlie addiction

Award Number: R01DA056358
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Behavior-based discovery of small-molecule modulators of neurochemical signaling pathways that underlie addiction - PROJECT SUMMARY 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $594,869 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Drug Use and Addiction Research Programs	000	3	5/17/2024	NON-COMPETING CONTINUATION	$594,869
														Subtotal = $594,869

Issue Date FY: 2023 ( Subtotal = $604,962 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Drug Use and Addiction Research Programs	000	2	5/26/2023	NON-COMPETING CONTINUATION	$604,962
														Subtotal = $604,962

Issue Date FY: 2022 ( Subtotal = $646,068 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Drug Use and Addiction Research Programs	000	1	7/13/2022	NEW	$646,068
														Subtotal = $646,068

Grand Total All Awards = $1,845,899

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Behavior-based discovery of small-molecule modulators of neurochemical signaling pathways that underlie addiction

Award Number: R01DA056358

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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