Targeting prefrontostriatal circuits to rescue alcohol-induced behavioral inflexibility
Active Project Grant Awarded Last action
- Award ID
- F31AA032134
- Recipient
-
University Of Maryland, Baltimore UEI Z9CRZKD42ZT1
- Awarding agency
-
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health, Department of Health and Human Services
- Obligated
- $81,248
Award facts
- Assistance listing
- 93.273 Alcohol Research Programs
- Completion date 1% complete
- Originally
- Place of performance
- Baltimore, MD 21201, USA
Award details come from USAspending.gov.
Description
- Abstract
- The progression of alcohol use disorder (AUD) is characterized by the emergence of inflexible behaviors, such as compulsive drinking, that exacerbate negative outcomes. Substantial evidence links behavioral inflexibility to hypoactivity of the prefrontal cortex, suggesting that deficient cognitive control over behavior drives compulsive drinking. Despite this, current AUD treatments do not address cognitive dysfunction, leaving inflexible behaviors unchecked. Importantly, chemogenetic activation of the dorsomedial prefrontal cortex prevents the progression of compulsive-like drinking in rats. This identifies a promising new avenue for therapeutic development: prefrontocortical disinhibition. Coupled with existing findings, my preliminary data suggest that negative allosteric modulation of Α5-subunit containing gabaa receptors (Α5GABAAR) may restore behavioral flexibility through disinhibitory action in the prefrontal cortex. To test this, i will implement an operant reversal-learning task to evaluate goal-directed behavior, a core component of behavioral flexibility (aim 1), and a quinine-challenge to evaluate inflexible, aversion-resistant drinking (aim 2). Both aims will utilize systemic administration of an Α5GABAAR negative allosteric modulator, to model clinical application, and local infusion to directly interrogate the role of prefrontocortical Α5GABAARS. Successful completion of these aims will validate prefrontocortical Α5 subunit-containing gabaa receptors as a promising, pro-cognitive drug target addressing inflexible behaviors in alcohol use disorder and other neuropsychiatric conditions characterized by cognitive dysfunction. This project expands upon the PI's existing expertise to provide training on animal behavior and in vivo pharmacological manipulations, which will optimize technical development as an independent researcher examining the cortical circuits driving behavioral flexibility.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $40,624 | |
| Amendment | $0 | |
| Original award | $40,624 |
Quick answers
Who received award F31AA032134?
F31AA032134 was awarded to University Of Maryland, Baltimore by National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health) on October 15, 2026.
How much is award F31AA032134 worth?
$81,248 has been obligated on F31AA032134.
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