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Diurnal Variation in Acetylcholine Modulation of Dopamine Dynamics Following Chronic Cocaine Intake

Award Number: F31DA058517
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/15/2023
PERIOD OF PERFORMANCE END DATE: 03/14/2025

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Diurnal Variation in Acetylcholine Modulation of Dopamine Dynamics Following Chronic Cocaine Intake - Project Summary In 2020, an estimated 5.2 million Americans reported using cocaine, with 1.3 million meeting criteria for Cocaine Use Disorder (CUD). Despite the increasing need, there are no FDA-approved treatments for CUD. One variable that is often overlooked in CUD research is the resulting disruption of circadian (24-hour) and diurnal (night/day) rhythms. Disrupted rhythms have been shown to prolong the cycle of cocaine abuse and increase the risk of relapse. CUD can be modeled with cocaine self-administration (SA) using three different patterns of cocaine intake: short continuous access (ShA), long continuous access (LgA), and intermittent access (IntA). Though our lab has established diurnal variation in rhythms of dopamine (DA) dynamics, including cholinergic interneuron (CIN) modulation and DA reuptake in naïve animals, it is not yet understood how adapting the type of cocaine SA intake pattern differentially affects these rhythms and the mechanistic pathways involved following long-term cocaine intake. The mesolimbic DA system in the nucleus accumbens core (NAc) is an important mediator of motivated and reward-associated behaviors that are maladapted in CUD. CINs are critical modulators of mesolimbic DA release in the NAc via their activation of acetylcholine (ACh) receptors on DA terminals. While the effects of chronic cocaine on DA signals and CIN/ACh activity have been studied extensively at single time points, a major obstacle in the field is that cocaine-induced changes in DA signaling rhythms and potential mechanisms for rhythmic disruptions, such as alterations in CIN signaling, have not been investigated. Thus, my central hypothesis is twofold: 1) to discover the effect of long-term, voluntary cocaine intake on time- of-day rhythms in DA and ACh NAc signaling, and 2) outline a mechanistic link between rhythms of ACh and DA signaling. The proposed research plan will examine the role of rhythms in DA release and CIN activity under various patterns of cocaine access with the following aims: (1) Assess the cocaine history and pattern of intake on diurnal variation in NAc DA release, (2) Examine a mechanism for disrupted diurnal rhythms in DA release in cocaine-exposed animals, and (3) Define the temporal architecture of CIN modulation of DA release magnitude in cocaine-exposed animals. These studies will highlight the importance of endogenous diurnal rhythms in NAc neurochemistry following chronic cocaine intake patterns to provide greater mechanistic insight into the role of rhythms in CUD. Understanding the influence of rhythms underlying CUD neurochemistry will provide novel treatment targets and propose times throughout the day in which to target them most effectively.


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 = -$4,451 )
2026	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	2	1/29/2026	NON-COMPETING CONTINUATION	-$4,451
														Subtotal = -$4,451

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	2	5/2/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	2	2/2/2024	NON-COMPETING CONTINUATION	$47,694
														Subtotal = $48,974

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	1	3/14/2023	NEW	$0
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	1	3/14/2023	NEW	$47,694
														Subtotal = $47,694

Grand Total All Awards = $92,217

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Diurnal Variation in Acetylcholine Modulation of Dopamine Dynamics Following Chronic Cocaine Intake

Award Number: F31DA058517

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/15/2023

PERIOD OF PERFORMANCE END DATE: 03/14/2025

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