Suellen Almeida-Correa, Fynn-Sebastian Wesemann, Sarah Diez, Mary Jane Maynard, Lucas Yebra Garcia, Patrizia Voehringer, Boris Ferger, Michael Becker, Carsten T. Wotjak, Johann du Hoffmann
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引用次数: 0
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.
期刊介绍:
Neuropsychopharmacology is a reputable international scientific journal that serves as the official publication of the American College of Neuropsychopharmacology (ACNP). The journal's primary focus is on research that enhances our knowledge of the brain and behavior, with a particular emphasis on the molecular, cellular, physiological, and psychological aspects of substances that affect the central nervous system (CNS). It also aims to identify new molecular targets for the development of future drugs.
The journal prioritizes original research reports, but it also welcomes mini-reviews and perspectives, which are often solicited by the editorial office. These types of articles provide valuable insights and syntheses of current research trends and future directions in the field of neuroscience and pharmacology.