Determining the role of MU opioid receptors in orbitofrontal cortex on reward and motivation

Active Project Grant Awarded Last action

Award ID
F31DA067300
Recipient
Awarding agency
Obligated
$50,114

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date 0% complete
Place of performance
St. Louis, MO 63110, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The primary goal of this nrsa F31 proposal is to determine how MU opioid receptors (moprs) in distinct orbitofrontal cortex (OFC) interneuron populations regulate reward valuation and behavioral flexibility. Dysfunctions in these computations are core features of opioid use disorder, obsessive-compulsive disorder, and depression, all of which involve impaired ability to update actions when outcomes change. While the OFC critically supports these processes, IT remains unknown how neuromodulators such as endogenous opioids shape local circuitry to influence behavior. Moprs are densely expressed on parvalbumin (PV) and somatostatin (SST) interneurons, two inhibitory cell types that exert complementary control over pyramidal neuron output, positioning them as powerful regulators of cortical computation. However, no study has determined how mopr signaling in specific interneuron populations affects OFC microcircuit function or decision-making. Using EX vivo patch-clamp electrophysiology, CRE-dependent crispr-CAS9 knockdown, and drugs acutely restricted by tethering (dart) approaches, i will causally test how moprs gate inhibitory control in PV versus SST interneurons. Aim 1 will define how moprs regulate the electrophysiological properties of these two interneuron populations. Aim 2 will determine how selective loss of moprs in PV or SST interneurons impacts motivated behaviors and cognitive flexibility. Aim 3 will oppositely assess how cell type-specific mopr stimulation biases performance on these same behaviors. This proposal will reveal how opioid signaling reshapes cortical computation at the level of defined inhibitory microcircuits, laying the foundation for targeted therapies that preserve adaptive decision-making while reducing compulsive drive. The proposed research and training plans provide rigorous training using high resolution and cutting edge techniques, which is complemented by structured development in fundamental neuromodulation biology and professional leadership. Together, these plans will uniquely position the applicant for an independent career studying neuromodulatory control of cognition in healthy and disease states.

Quick answers

Who received award F31DA067300?

F31DA067300 was awarded to The Washington University by National Institute on Drug Abuse (National Institutes of Health) on February 2, 2027.

How much is award F31DA067300 worth?

$50,114 has been obligated on F31DA067300.

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