Effort, timing and choice: a refined rodent effort choice task with excellent sensitivity to dopamine modulators

Neuropsychopharmacology. 2026 Jun 10. doi: 10.1038/s41386-026-02453-8. Online ahead of print.

ABSTRACT

Motivational deficits and anhedonia are core features of psychiatric disorders such as depression, schizophrenia and addiction, yet current treatments rarely improve these symptoms. Progress towards targeted therapeutics requires preclinical tasks that reliably capture pharmacological modulation of relevant neural circuits. Here, we developed a modified effort-related choice task (mERC) that integrates high effort demands, extended intertrial intervals and choice, to enable robust bidirectional sensitivity to systemic pharmacology. Unlike standard paradigms, mERC detects both impairing and enhancing effects of dopamine modulators within a single task and reveals drug-sensitive anticipatory responses during intertrial intervals-a behavioral feature linked to interval timing and motivational vigor. Using neurochemical and photometric analyses, we show that mERC performance is associated with behavioral signatures consistent with dopaminergic signaling across different timescales and is potentially constrained by a bounded dynamic range beyond which behavioral modulation is lost. Species differences in drug efficacy map onto baseline dopamine tone and depletion dynamics, underscoring the interactions between task structure and neurochemical state. Together, these findings establish mERC as a stable and sensitive preclinical assay for enhancing our understanding of effort-based decision-making and for screening novel therapeutics targeting motivational dysfunction.

PMID:42270782 | DOI:10.1038/s41386-026-02453-8