# Preclinical neurophysiological and behavioral assays of motivation and effort

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $391,694

## Abstract

PROJECT SUMMARY
 Deficits in motivation and effort (i.e., avolition) are defining characteristics of several psychiatric and
neurological disorders; have adverse effects on functional recovery, disease chronicity, and morbidity; and lack
effective treatments. Research and development of novel treatments for avolition has been hindered by the
lack of well-validated functional measures of target engagement that are similar across human and non-human
model species, possibly due to the use of different approaches in laboratory animals and humans that lack
translation. Importantly, neurophysiological recordings enable direct observation of synchronized neural activity
with high (ms) temporal resolution and are argued to have higher validity for cross-species comparison of the
effects of drugs on behavior compared to cellular or molecular measures. In this regard, and in line with RFA-
MH-19-235 and the NIMH RDoC initiative, the current application proposes to optimize, evaluate, and
mechanistically test neurophysiological and behavioral assays of physical and cognitive effort in a manner that
will enable preclinical pipelines to develop novel and efficacious treatments for avolition in clinical populations
 In Aim 1, we will optimize rodent behavioral assessments of physical and cognitive effort using the
physical effort task (PET) task and cognitive effort task (CET), respectively. Combined behavioral and
electrophysiological evaluation will determine the neural substrates of physical and cognitive effortful decision
making. In Aim 2, we will validate these models using pharmacological challenges (modafinil and tolcapone) to
potentiate the behavioral and neurophysiological correlates of effortful decision making. Finally, in Aim 3, we
will investigate the mesostriatal and mesocortical mechanisms underlying drug-induced potentiation of effortful
decision making using a combination of optogenetic manipulations in genetically defined neurons,
electrophysiological recording, and behavioral pharmacology. Collectively, this application will delineate the
precise contributions of mesolimbic and mesocortical dopamine circuits in the mediation of different forms of
effortful behavior, identifying neural substrates that can be targeted to ameliorate impairments in motivation
that are core to several psychiatric and neurological disorders.

## Key facts

- **NIH application ID:** 10439637
- **Project number:** 5R01MH121352-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ANDRE DER-AVAKIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,694
- **Award type:** 5
- **Project period:** 2019-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439637

## Citation

> US National Institutes of Health, RePORTER application 10439637, Preclinical neurophysiological and behavioral assays of motivation and effort (5R01MH121352-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10439637. Licensed CC0.

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