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Nicotinic and Insular Cortical Mechanisms Contributing to Opiate Misuse

Award Number: K01DA048336
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Nicotinic and Insular Cortical Mechanisms Contributing to Opiate Misuse - Project Summary/Abstract Concurrent nicotine use is highly implicated in the propensity to misuse prescribed opiates, future development of opiate dependence, and susceptibility to accidental opiate overdose. Approximately 83-95% of patients involved in opioid treatment programs are tobacco users. As such, there exists a clear public health mandate for elucidation of mechanisms contributing to opiate addiction liability resultant from opiate and nicotine polysubstance use. The anterior insular cortex is heavily involved in processing the interoceptive stimulus properties of commonly abused drugs and insular dysfunction is implicated in the development and maintenance of substance use disorders. The role of the insular cortex in opiate addiction, and furthermore, how nicotine may play a role, is currently underexplored. There is emerging evidence that nicotine interferes with insular function, specifically through depressing synaptic potentiation and inhibiting the output of the insular cortex. Preliminary data demonstrate that nicotine delivered to the anterior insular cortex interferes with the processing of the stimulus properties of opiates in a quantitative manner, an effect remarkably similar to insular chemogenetic inactivation. Specifically, subjects either administered nicotine or undergoing chemogenetic inactivation of the insular cortex behave as if they have received a lower dose of morphine relative to controls in paradigms examining both the reinforcing (conditioned place preference; CPP) and aversive (conditioned taste avoidance; CTA) stimulus properties of opiates. As a result, tobacco smokers may require more and stronger doses of opiates in order to achieve the desired effects. This reduced sensitivity to the stimulus properties of opiates due to nicotine co-use may facilitate the development of opiate dependence. The goal of this project is to elucidate the mechanisms and neural circuits through which insular cortical nicotinic activity contributes to enhanced opiate addiction liability. These experiments will employ a combination of psychophysical behavioral measures, site-specific behavioral pharmacology, circuit-specific chemogenetic manipulation, and in vivo electrophysiology in order to fully characterize the mechanisms through which insular cortical nicotinic activity may contribute to the development of opiate substance use disorders. Furthermore, through completion of these proposed studies, the applicant will be competently trained in new technical skills and perspectives, ultimately facilitating a successful transition to a principal investigator conducting programmatic research on the comorbidity of nicotine and opiate abuse.


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 = $0 )
2026	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	5	12/4/2025	SUPPLEMENT FOR EXPANSION	-$39,962
2026	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	001	5	12/18/2025	SUPPLEMENT FOR EXPANSION	$39,962
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $39,962 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	5	7/25/2024	SUPPLEMENT FOR EXPANSION	$39,962
														Subtotal = $39,962

Issue Date FY: 2023 ( Subtotal = $169,020 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	5	7/17/2023	NON-COMPETING CONTINUATION	$169,020
														Subtotal = $169,020

Issue Date FY: 2022 ( Subtotal = $169,020 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	4	7/18/2022	NON-COMPETING CONTINUATION	$169,020
														Subtotal = $169,020

Issue Date FY: 2021 ( Subtotal = $169,020 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	3	7/23/2021	NON-COMPETING CONTINUATION	$169,020
														Subtotal = $169,020

Issue Date FY: 2020 ( Subtotal = $169,020 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	001	2	7/17/2020	NON-COMPETING CONTINUATION	$169,020
2020	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	1	4/1/2020	NEW	$0
														Subtotal = $169,020

Issue Date FY: 2019 ( Subtotal = $144,368 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Drug Use and Addiction Research Programs	000	1	6/25/2019	NEW	$144,368
														Subtotal = $144,368

Grand Total All Awards = $860,410

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Nicotinic and Insular Cortical Mechanisms Contributing to Opiate Misuse

Award Number: K01DA048336

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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