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Contribution of BLA-mPFC pathway to risky choice and compulsive cocaine seeking

Award Number: R15DA047610
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Contribution of BLA-mPFC pathway to risky choice and compulsive cocaine seeking - Project Summary/Abstract This is a resubmission of a renewal application for an AREA R15 grant to continue research funded in DA047610 (“Contribution of NMDA NR2B subunit to risky choice and economic demand for cocaine” now titled “Contribution of BLA-mPFC pathway to risky choice and compulsive cocaine seeking”). The purpose of the R15 grant is to stimulate research at primarily educational institutions like Northern Kentucky University (NKU) that support baccalaureate training but are not recipients of major NIH support. Risky choice is characteristic of several psychiatric conditions, including substance use disorders (SUDs). Substance misuse can be considered a risky behavior as individuals can become incarcerated for their drug use or can ultimately die from overdose. Understanding the neurobiology of risky choice is important for designing effective treatment interventions for individuals that are at risk for developing SUDs. During our current funding period, we have shown that the GluN2B subunit of the glutamate N-methyl-D-aspartate (NMDA) receptor mediates risky choice as assessed in the risky decision task (RDT), and it mediates addiction-like behaviors as measured in cocaine self-administration and in methamphetamine conditioned place preference. Because the RDT uses foot shock as punishment, determining if a rat displays increased risky choice or insensitivity to shock is difficult. Thus, the first goal of the current proposal is to use a novel task to measure risky choice. To this end, rats will be tested in an equivalent expected value (EEV) task, in which reinforcer magnitude and reinforcement probability will be adjusted across concurrently available reinforcers such that the expected utility (value) of each alternative is equivalent. Because the expected value is equivalent across reinforcer alternatives, there is no suboptimal choice. However, risky choice can be measured by the percentage of responses for the lower probability/larger reward alternative. To further elucidate the neurocircuitry of risky choice, we will determine if chemogenetic inhibition of medial prefrontal cortex (mPFC)-projecting basolateral amygdala (BLA) neurons and/or BLA- projecting mPFC neurons decreases risky choice in the EEV task (Specific Aim 1). Specific Aims 2 and 3 will utilize the same chemogenetic approach from Specific Aim 1 to determine if the reciprocal connections between the BLA and the mPFC mediate compulsive cocaine seeking and resurgence of cocaine seeking (model of relapse-like behavior). Renewed funding will allow us to answer these critical questions and will allow undergraduate students to continue gaining research experience in behavioral neuroscience research at NKU.


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 = $0 )
2024	2023	NORTHERN KENTUCKY UNIV	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	001	2	9/23/2024	COMPETING CONTINUATION	$4,742
2024	2021	NORTHERN KENTUCKY UNIV	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	000	1	9/23/2024	SUPPLEMENT FOR EXPANSION	-$4,742
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $420,000 )
2023	2023	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	002	2	6/19/2023	COMPETING CONTINUATION	$0
2023	2023	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	000	2	5/17/2023	COMPETING CONTINUATION	$420,000
2023	2019	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	001	1	5/26/2023	NEW	$0
														Subtotal = $420,000

Issue Date FY: 2021 ( Subtotal = $12,012 )
2021	2021	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	001	1	5/27/2021	SUPPLEMENT FOR EXPANSION	$352
2021	2021	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	000	1	5/21/2021	SUPPLEMENT FOR EXPANSION	$11,660
														Subtotal = $12,012

Issue Date FY: 2019 ( Subtotal = $397,500 )
2019	2019	NORTHERN KENTUCKY UNIVERSITY	NUNN DR	NEWPORT	KY	41099	CAMPBELL	USA	Drug Use and Addiction Research Programs	000	1	5/24/2019	NEW	$397,500
														Subtotal = $397,500

Grand Total All Awards = $829,512

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Contribution of BLA-mPFC pathway to risky choice and compulsive cocaine seeking

Award Number: R15DA047610

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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