EFFORT, TIMING AND CHOICE: A REFINED RODENT EFFORT CHOICE TASK WITH EXCELLENT SENSITIVITY TO DOPAMINE MODULATORS

Anhedonia and reduced motivation are core symptoms of disorders such as depression, schizophrenia, and addiction. Current treatments, including SSRIs and SNRIs, often improve mood but insufficiently address these deficits, highlighting a critical need for targeted therapies. Developing effective new treatments requires robust preclinical tools to validate drug targets and assess efficacy. Therefore, tasks with behavioral readouts that reliably reflect pharmacological modulation of specific neural circuits and neurotransmitter systems are essential. Here, we present a modified Effort-Related Choice task (mERC) for rats and mice, demonstrating precise bidirectional sensitivity and dose-dependent responses to systemically administered drugs that modulate dopamine signaling. Using an integrative approach — microdialysis, fiberphotometry, and MALDI-MSI — we show that mERC behavior closely mirrors pharmacologically induced changes in dopamine tone. Notably, mERC also captures drug-induced changes in anticipatory responding during intertrial intervals, a behavior linked to internal timing and motivational vigor which are disrupted in neuropsychiatric patients. These anticipatory responses reduce response latency and increase reward acquisition, providing additional relevant pre-clinical measures of motivational enhancement by novel pharmacotherapies. Our results support mERC as a sensitive and potentially translational tool for assessing motivational deficits and pharmacologic modulation, advancing the development of targeted treatments for neuropsychiatric disorders.