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The effect of adolescent drug-induced neuroimmune signaling in sex-specific social development and reward learning.

Award Number: R01DA052889
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The effect of adolescent drug-induced neuroimmune signaling in sex-specific social development and reward learning. - PROJECT SUMMARY Substance use disorders (SUDs), particularly those involving opioids, have reached epidemic levels. SUDs are hypothesized to be learning and memory disorders: the association of drug ‘reward’ with otherwise neutral stimuli promotes continued or reinstated drug use (relapse) when similar stimuli are re-encountered. Relapse rates are 40-60%, suggesting that previously learned drug associations are a constant risk for those recovering from SUDs. Socially-mediated learning is ubiquitous across species, and social factors also modulate drug use. However, how social factors influence drug-associated learning, and its expression once established, is unclear. The nucleus accumbens (NAc) reward region is critical for both drug associative learning and for social influence over behavior. We determined that microglia, the resident immune cells of the brain, mediate social development via phagocytosis, or “pruning,” of synaptic proteins in the NAc core during early adolescence in male rats, and pre-adolescence in females. Adolescent drug use increases SUD risk and social dysfunction later in life; in fact, even prescription opioid use in adolescence increases opioid misuse later in life. The opioid morphine directly activates a pro-phagocytic receptor on microglia, including on NAc microglia. These data raise the possibility that adolescent opioid use increases SUD risk by changing microglia-mediated NAc and social development, and in turn social influence over reward learning. In this proposal, we will restrict short-term morphine exposure to each sex-specific NAc core pruning period in adolescence to determine (1) how morphine affects ongoing developmental synaptic pruning activity, (2) social development, and (3) socially-mediated reward learning. Our core hypothesis is that adolescent morphine exposure exacerbates microglia-mediated pruning in the NAc core, causing abnormal social development and increased social influence over reward learning. This proposal will be the first to examine a mechanistic relationship between social development in adolescence and reward learning in adulthood, and may identify sex- specific adolescent periods of vulnerability during which lifetime SUD risk and other mental health disorders can be influenced.


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: 2025 ( Subtotal = $469,353 )
2025	2025	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	000	4	4/28/2025	NON-COMPETING CONTINUATION	$469,353
														Subtotal = $469,353

Issue Date FY: 2024 ( Subtotal = $523,143 )
2024	2024	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	001	3	4/25/2024	NON-COMPETING CONTINUATION	$52,315
2024	2024	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	000	3	3/22/2024	NON-COMPETING CONTINUATION	$470,828
														Subtotal = $523,143

Issue Date FY: 2023 ( Subtotal = $507,122 )
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	000	2	4/10/2023	NON-COMPETING CONTINUATION	$507,122
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	001	2	5/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $507,122

Issue Date FY: 2022 ( Subtotal = $486,666 )
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Drug Use and Addiction Research Programs	000	1	6/3/2022	NEW	$486,666
														Subtotal = $486,666

Grand Total All Awards = $1,986,284

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The effect of adolescent drug-induced neuroimmune signaling in sex-specific social development and reward learning.

Award Number: R01DA052889

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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