Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role of prelimbic cortical endocannabinoid signaling in enhanced cocaine-seeking behavior following combined repeated stress and cocaine use in rats

Award Number: R37DA057944
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

Role of prelimbic cortical endocannabinoid signaling in enhanced cocaine-seeking behavior following combined repeated stress and cocaine use in rats - Project summary/Abstract Addiction remains a vast problem in the United States and complicating the issue is the lack of FDA-approved medications for the treatment of cocaine use disorder (CUD) making it a critical unmet need. A difficulty in identifying treatment options is that CUD is multi-faceted involving interactions among several external factors, including stress, which is unavoidable in daily life. Despite the prevalence of stress in human populations of CUD, most pre-clinical addiction research does not incorporate stress as a factor during periods of drug use. To examine the importance of stress-cocaine interactions on cocaine use and seeking behavior we use a model where, in rats demonstrating otherwise stable cocaine self-administration (SA), a stressor delivered daily at the time of cocaine SA, escalates cocaine intake and enhances cocaine-seeking behavior. This likely involves neurobiological mediators that connect stress-responsive and reward systems in the brain, such as endocannabinoid signaling (eCB). In support of this, systemic administration of a cannabinoid receptor 1 antagonist attenuates cocaine-induced reinstatement only in rats with a history of stress. Furthermore, we have localized this effect to the prelimbic cortex (PrL), a key site for regulation of stress and drug-seeking behavior. Importantly, eCB signaling, through attenuation of inhibitory neurotransmission, is well positioned to regulate PrL pyramidal neuron activity and output which ultimately results in expression of enhanced cocaine-seeking behavior. This proposal tests the novel hypothesis that repeated stress at the time of cocaine SA produces long-lasting upregulation of eCB signaling in the PrL leading to increased pyramidal neuron activity and drug- seeking behavior through dysregulated GABAergic signaling. To test this hypothesis, we will use behavioral, molecular, and neurophysiological techniques to assess the involvement of PrL eCB signaling in the long-term consequences of repeated stress-cocaine interactions. First, we will assess the role of PrL eCB signaling, via pharmacological manipulation, in enhanced cocaine-induced reinstatement in stress-escalated rats. We will then identify how combined repeated stress and cocaine SA regulates PrL eCB signaling by quantifying cell type-specific changes in molecular components of the eCB system using fluorescent in situ hybridization, and measure changes in PrL eCB content with mass spectrometry following cocaine-induced reinstatement. Lastly, we will examine changes in eCB-mediated inhibitory synaptic plasticity that are associated with enhanced cocaine-induced reinstatement, using whole-cell patch clamp recordings in the PrL. We will also use in vivo fiber photometry measurement of Ca2+signaling to identify the contribution of eCB signaling to changes in PrL pyramidal neuron activity associated with enhanced cocaine-induced reinstatement. These studies will provide much needed information about how stress-drug interactions regulate prefrontal cortical circuits and has treatment implications for those with CUD, especially for those for whom stress is a predominant contributing factor by identifying unique neurobiological mechanisms that may provide therapeutic targets.


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 = $410,889 )
2026	2026	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	001	3	2/6/2026	NON-COMPETING CONTINUATION	$41,089
2026	2026	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	000	3	1/30/2026	NON-COMPETING CONTINUATION	$369,800
														Subtotal = $410,889

Issue Date FY: 2025 ( Subtotal = $392,421 )
2025	2025	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	001	2	1/24/2025	NON-COMPETING CONTINUATION	$353,178
2025	2025	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	002	2	4/8/2025	NON-COMPETING CONTINUATION	$39,243
2025	2024	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	000	1	11/6/2024	NEW	$0
														Subtotal = $392,421

Grand Total All Awards = $803,310

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of prelimbic cortical endocannabinoid signaling in enhanced cocaine-seeking behavior following combined repeated stress and cocaine use in rats

Award Number: R37DA057944

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer