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

Active Project Grant Awarded Last action

Award ID
R01DA052889
Recipient
Awarding agency
Obligated
$5,474,953

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date 78% complete
Originally
Funding
  • $4,988,287.00 Federal
  • $486,666.00 Non-federal
Place of performance
Albany, NY 12208, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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.

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Subawards

Subrecipient Amount Awarded
Trustees Of Boston University The subaward will assist with establishing social facilitation of drug memory reinstatement experiments including sharing protocols, engaging in discussions… $14,208
The Trustees Of Davidson College Subaward will provide guidance, technical expertise, and intellectual input regarding the interpretation of social influences over reward learning, including… $15,582
The Trustees Of Davidson College Provide guidance, technical expertise, and intellectual input regarding the interpretation of social influences over reward learning, including sharing… $45,396
Trustees Of Boston University In this project, Trustees of Boston University will assist with establishing social facilitation of drug memory reinstatement experiments including sharing… $40,614

Quick answers

Who received award R01DA052889?

R01DA052889 was awarded to Albany Medical College by National Institute on Drug Abuse (National Institutes of Health) on July 1, 2022.

How much is award R01DA052889 worth?

$5,474,953 has been obligated on R01DA052889: $4,988,287 in federal funding and $486,666 in non-federal funding.

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