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Investigating New Roles for Orphan GPCRs in Opioid Actions

Award Number: F32DA047771
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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Investigating New Roles for Orphan GPCRs in Opioid Actions - Project Summary / Abstract Opioid addiction and accidental overdose have emerged as significant health crises in the last decade as the prevalence and availability of this highly addicting class of drugs have dramatically increased. Opioids are agonists for the mu opioid receptor (MOR), which in addition to blocking pain signaling, also mediates the development of unwanted side effects including tolerance and with continued usage, dependence. MOR signaling is endogenously regulated downstream of the receptor to terminate or tune signaling and to thus modulate the physiological effects of opioids. Current strategies to curtail opioid side effects include therapeutic targeting / modulating activation of known MOR regulators such as b-arrestin and regulators of G protein signaling (RGS). Still, there is no comprehensive list of MOR regulators. Using an unbiased genetic screen, we recently uncovered a novel orphan G protein-coupled receptor (GPCR) signaling pathway in the brain that demonstrates an anti-opioid phenotype in two independent animal models. Further, the orphan receptor is co- localized with MOR in key areas of the brain involved in analgesia and reward. Yet, this novel pathway and how it may regulate MOR is wholly undefined. The proposed project will test the hypothesis that the orphan GPCR pathway is a negative regulator of MOR with therapeutic potential to mitigate the unwanted side effects of opioids. To test this hypothesis, biosensor-based cellular assays will be employed to examine classical MOR signaling and how it is altered by dynamic activation of the orphan GPCR pathway. Additionally, the signaling emanating from the orphan GPCR will be determined to further uncover how the signaling pathways endogenously interact. Finally, the ability of the orphan GPCR to decrease opioid side effects will be determined in mouse models of opioid-related behaviors. Taken together, this work will delineate a novel anti-opioid signaling pathway that could find clinical use to lessen negative opioid-related side effects.


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: 2023 ( Subtotal = $0 )
2023	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	002	3	1/19/2023	NON-COMPETING CONTINUATION	$0
2023	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	001	2	1/19/2023	NON-COMPETING CONTINUATION	$0
2023	2019	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	000	1	1/19/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $5,872 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	000	3	2/19/2021	NON-COMPETING CONTINUATION	$70,458
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	001	3	5/4/2021	NON-COMPETING CONTINUATION	-$64,586
														Subtotal = $5,872

Issue Date FY: 2020 ( Subtotal = $67,446 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	000	2	3/25/2020	NON-COMPETING CONTINUATION	$67,446
														Subtotal = $67,446

Issue Date FY: 2019 ( Subtotal = $61,610 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	001	1	3/8/2019	NEW	$0
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Drug Use and Addiction Research Programs	000	1	3/8/2019	NEW	$61,610
														Subtotal = $61,610

Grand Total All Awards = $134,928

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Investigating New Roles for Orphan GPCRs in Opioid Actions

Award Number: F32DA047771

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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