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Investigations into extended amygdalar cholecystokinin for cocaine-related sleep disturbances and sleep-dependent cocaine memories

Award Number: F32DA065350
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/19/2027
PERIOD OF PERFORMANCE END DATE: 01/18/2028

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Investigations into extended amygdalar cholecystokinin for cocaine-related sleep disturbances and sleep-dependent cocaine memories - PROJECT SUMMARY Sleep is an integral homeostatic process that allows for physiological recovery and supports emotional and cognitive processes. Sleep disturbances have been shown to produce adverse effects on memory consolidation, which is a critical mechanism that mediates decision-making and other behaviors when awake. Dysregulated sleep patterns are commonly seen in individuals with a substance use disorder. It is also well-established that substance dependence is, in part, the result of maladaptive decisions to seek and take drugs. Thus, impairments in decision-making seen in substance use disorders that lead to aberrant drug use may potentially be due to disturbances in sleep homeostasis and sleep-mediated drug memories. Identifying a multifunctional neural substrate involved in regulating sleep, memory, and substance use would be key to furthering our understanding of how these behavioral interactions give rise to persistent substance abuse and inform future treatment approaches. The bed nucleus of stria terminalis (BNST) contains a variety of distinct, neuropeptide-expressing neurons that serve functions in a range of behaviors, including stress and emotional arousal. The proposed study will investigate the involvement of a heavily understudied subpopulation of GABAergic neurons in the BNST, those expressing cholecystokinin (CCKBNST), for regulating sleep homeostasis and sleep-dependent drug memories. Using bulk calcium imaging to measure in vivo activity of CCKBNST neurons aligned to simultaneous polysomnographic recordings to monitor sleep-wake patterns, the first aim will examine the activity profile of CCKBNST neurons during cocaine withdrawal-induced dysregulated sleep, and how these sleep and neuronal activity dynamics evolve across discrete withdrawal time points. The second aim will employ chemogenetic inhibition of CCKBNST neurons to determine their necessity in promoting sleep under normal and disrupted sleep homeostasis. This will reveal a potential mechanism by which CCKBNST neurons are contributing to sleep-wake regulation. The third and final aim will elucidate the involvement of CCKBNST neurons in cocaine-seeking via sleep-dependent drug memories by examining neuronal reactivation patterns following exposure to a cocaine- related context and using targeted optogenetic manipulations during sleep-mediated memory consolidation to either strengthen or weaken cocaine seeking. Collectively, the outcomes from this proposal will provide novel and valuable insight about the role of CCKBNST neurons in maladaptive drug seeking and serve as impetus for further research characterizing this promising neural substrate in the development of treatments for substance dependence, targeting sleep disturbances and memory processes underpinning cue-induced relapse.


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 = $76,780 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Use and Addiction Research Programs	000	1	7/22/2026	NEW	$76,780
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Drug Use and Addiction Research Programs	001	1	7/23/2026	NEW	$0
														Subtotal = $76,780

Grand Total All Awards = $76,780

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Investigations into extended amygdalar cholecystokinin for cocaine-related sleep disturbances and sleep-dependent cocaine memories

Award Number: F32DA065350

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/19/2027

PERIOD OF PERFORMANCE END DATE: 01/18/2028

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