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Modulation of the Perineuronal Net Protein Brevican in the Nucleus Accumbens, and its Impact on Addiction-related Behavior

Award Number: F31DA049442
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary Psychostimulant drugs of abuse induce persistent functional changes in the neural reward circuitry that underlie the development of addiction. These regions include the nucleus accumbens (NAc), a key area for drug reward. Growing evidence suggests that altered interneuron function in NAc makes key contributions to the drug-induced circuit adaptations leading to addiction behaviors. We have shown that NAc parvalbumin- expressing (PV+) inhibitory interneurons are required for multiple addiction-related behaviors in mice, including amphetamine (AMPH)-induced locomotor sensitization and conditioned place preference (CPP). Others have shown that cocaine self-administration strengthens excitatory inputs from basolateral amygdala onto NAc PV+ interneurons, and artificially potentiating these synapses accelerates acquisition of cocaine self-administration in naïve mice, suggesting that synaptic plasticity in NAc PV+ interneurons is behaviorally relevant for the development of addiction-like behaviors. However, little is known about the molecular mechanisms by which psychostimulants alter PV+ inhibitory interneuron function, and how this contributes to addictive behaviors. A promising mechanistic target is the perineuronal net protein Brevican (Bcan), which plays a cell-autonomous role in stabilizing excitatory inputs onto PV+ interneurons. The overarching goal of this proposal is to test the hypothesis that repeated psychostimulant exposure modulates PV+ interneuron activity through regulation of Bcan expression. In Aim 1 I will characterize the regulation of Bcan expression in NAc PV+ interneurons over the development of AMPH CPP. In Aim 2 I will test how manipulating Bcan expression affects the synaptic inputs to these neurons. In Aim 3 I will test the effect of manipulating Bcan in NAc PV+ cells on the threshold to develop CPP. These studies will investigate cellular transcriptional and synaptic plasticity mechanisms within PV+ interneurons, and how they affect the expression of addiction-related behaviors.


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 = -$731 )
2024	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	3	12/28/2023	NON-COMPETING CONTINUATION	-$731
														Subtotal = -$731

Issue Date FY: 2023 ( Subtotal = -$15,376 )
2023	2022	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	3	3/14/2023	NON-COMPETING CONTINUATION	-$15,376
														Subtotal = -$15,376

Issue Date FY: 2022 ( Subtotal = $38,783 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	3	6/14/2022	NON-COMPETING CONTINUATION	$38,783
														Subtotal = $38,783

Issue Date FY: 2021 ( Subtotal = $38,067 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	2	6/16/2021	NON-COMPETING CONTINUATION	$38,067
														Subtotal = $38,067

Issue Date FY: 2020 ( Subtotal = $37,551 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	1	6/5/2020	NEW	$37,551
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Drug Abuse and Addiction Research Programs	001	1	6/5/2020	NEW	$0
														Subtotal = $37,551

Grand Total All Awards = $98,294

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Modulation of the Perineuronal Net Protein Brevican in the Nucleus Accumbens, and its Impact on Addiction-related Behavior

Award Number: F31DA049442

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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