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Transcriptomic single-cell profiling in breathing-specific parabrachial mu-opioid receptor neurons

Award Number: R01DA056658
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Transcriptomic single-cell profiling in breathing-specific parabrachial mu-opioid receptor neurons - ABSTRACT Opioids are the most commonly used and most effective analgesics, and are the first line of defense against acute and severe pain. However, this dramatic ability to mitigate pain comes with many side effects. These include constipation, nausea, sedation, dizziness, respiratory depression, dependence, and addiction. Among these, respiratory depression is the major driver of death by opioid overdose. According to the Center for Disease Control (CDC), nearly 50,000 people died in 2019 by opioid-induced respiratory depression (OIRD) in the United States, and the death rate is rising rapidly due to increased misuse and addiction to both prescription and illicit opioids. Thus, the US is currently experiencing a serious national public health crisis that is also taking a toll on social economic welfare. Despite these dire numbers, research elucidating the neural mechanisms of OIRD, which could identify therapeutic targets, has not been rigorously investigated. Animal studies have shown that OIRD and opioid analgesia are both mediated by the µ-opioid receptor (MOR), however the neural circuits and brain regions responsible for OIRD and opioid analgesia are not fully understood. The proposed research aims to dissect the neural circuits that selectively mediate OIRD or opioid analgesia using cutting-edge molecular, physiological, behavioral, and imaging techniques. Projection-specific single-cell transcriptomic analysis will then be used to identify functional markers expressed in the MOR- expressing neurons that specifically mediate OIRD, not opioid analgesia. Successful completion of the proposed research will identify novel therapeutic targets that selectively rescue OIRD without altering analgesic effects of opioids.


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: 2026 ( Subtotal = $668,659 )
2026	2026	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	5	5/26/2026	NON-COMPETING CONTINUATION	$668,659
														Subtotal = $668,659

Issue Date FY: 2025 ( Subtotal = $668,659 )
2025	2025	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	4	5/21/2025	NON-COMPETING CONTINUATION	$668,659
														Subtotal = $668,659

Issue Date FY: 2024 ( Subtotal = $668,659 )
2024	2024	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	3	7/18/2024	NON-COMPETING CONTINUATION	$0
2024	2024	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	3	5/22/2024	NON-COMPETING CONTINUATION	$668,659
														Subtotal = $668,659

Issue Date FY: 2023 ( Subtotal = $742,953 )
2023	2023	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	2	5/10/2023	NON-COMPETING CONTINUATION	$742,953
														Subtotal = $742,953

Issue Date FY: 2022 ( Subtotal = $742,953 )
2022	2022	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	1	7/5/2022	NEW	$742,953
														Subtotal = $742,953

Grand Total All Awards = $3,491,883

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Transcriptomic single-cell profiling in breathing-specific parabrachial mu-opioid receptor neurons

Award Number: R01DA056658

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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