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Characterizing BLA dopaminergic and glutamatergic mechanisms of dynamic drug seeking

Award Number: F31DA060004
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/12/2024
PERIOD OF PERFORMANCE END DATE: 02/11/2027

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Characterizing BLA dopaminergic and glutamatergic mechanisms of dynamic drug seeking - PROJECT SUMMARY Relapse and craving in addiction are heavily controlled by environmental cues that evoke dynamic motivational states and reinforce actions. Both the basolateral amygdala (BLA) and dopamine (DA) signaling are critical for associative learning processes and cue-driven motivational states. The BLA receives dense dopaminergic projections and is enriched with D1 DA receptors (D1DRs), however BLA DA functions in addiction remain largely unexplored. Presentations of cocaine-predictive stimuli increase extracellular DA levels and activate neurons within the amygdala, while BLA D1DRs influence drug-seeking behaviors and their activation increases excitability of BLA principal neurons - a major target of DA inputs into the BLA. As there are extensive excitatory projections from the BLA to the nucleus accumbens (NAc), if BLA DA and D1-neurons are underlying facets of state dynamics-driven drug seeking behaviors, synaptic strength within this pathway may be uniquely potentiated following binge-like cocaine seeking. Understanding the role of BLA activity and DA signaling in drug seeking will reveal novel insight into the brain circuitry that drives emotional learning and addiction-related behaviors to provide a strong scientific framework for investigating mechanisms underlying affective diseases. This proposal will make use of new tools to record and manipulate DA and D1 neurons in the amygdala to investigate their contributions to dynamic cocaine seeking behaviors (Aim 1) and investigate how binge-like cocaine self-administration impacts the functional connectivity of glutamatergic BLA to NAc circuits (Aim 2). First, I will measure in vivo DA signaling and D1-neuron activity in the BLA during cocaine self-administration using fiber photometry to test the hypothesis that BLA DA transmission and D1-neuron activity will track the emergence of dynamic, sensory-guided drug seeking motivational states. I will also optogenetically inhibit BLA D1-neurons during the same paradigm to investigate if BLA D1-neurons play a necessary role in state-level control of binge-like drug seeking. Finally, in an ex vivo preparation, I will use optogenetics to stimulate the terminals of glutamatergic BLA projection neurons in an NAc slice while recording the resulting local field potentials after rats undergo cocaine self-administration. These studies will test the hypothesis that BLA-NAc excitatory synaptic strength will be modulated by the pattern of drug use history via drug state-intermittency information from the BLA. This proposal will establish fundamental principles by which dopaminergic and glutamatergic mechanisms interact within the amygdalostriatal system to influence the emergence and control of dynamic drug-seeking motivational states.


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 = $49,538 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Drug Use and Addiction Research Programs	000	3	1/28/2026	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $49,538

Issue Date FY: 2025 ( Subtotal = $48,596 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Drug Use and Addiction Research Programs	000	2	1/9/2025	NON-COMPETING CONTINUATION	$48,032
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Drug Use and Addiction Research Programs	001	2	8/11/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $48,596

Issue Date FY: 2024 ( Subtotal = $46,664 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Drug Use and Addiction Research Programs	001	1	1/30/2024	NEW	$0
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Drug Use and Addiction Research Programs	002	1	4/30/2024	NEW	$1,280
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Drug Use and Addiction Research Programs	000	1	1/30/2024	NEW	$45,384
														Subtotal = $46,664

Grand Total All Awards = $144,798

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Characterizing BLA dopaminergic and glutamatergic mechanisms of dynamic drug seeking

Award Number: F31DA060004

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/12/2024

PERIOD OF PERFORMANCE END DATE: 02/11/2027

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