A Dual Effort Choice paradigm reveals pharmacological divergence between intrinsic and extrinsic motivation within the same task environment

Abstract

Motivation loss is a transdiagnostic symptom, prevalent across neuropsychiatric and neurodegenerative diseases. Current treatments fail to effectively treat this symptom domain, giving it significant clinical importance. The fields of neuroscience and drug development have primarily focused on extrinsic motivation, whereby an animal must perform an action to receive an external food or water-based reward. However, many of our everyday activities are facilitated by intrinsic motivation, where completing an action is inherently rewarding. By utilising tasks focused only on extrinsic motivation, we may miss critical neurobiological and therapeutic differences between motivation types. Previous work has shown divergence in drug effect between extrinsic and intrinsic motivation tasks across a wide range of clinically-used drugs, indicating translationally-relevant differences across motivation domains that warrant further study. Therefore, the aim of this work was first to develop a task capable of simultaneously quantifying intrinsic and extrinsically motivated behaviour within the same task environment. Secondly, to use this task to further investigate this neurochemical divergence by examining a wide range of clinically-relevant drugs within this new task context. Here, we find that a pharmacological reduction in dopaminergic signalling reduced motivation across both extrinsic and intrinsic options within the new task, though this effect was mechanism dependent. In contrast, acute serotonergic and dopaminergic signalling increase produced a more heterogenous pattern, indicating nuanced mechanistic differences even when presented in the same task environment. Therefore, this task provides a new approach for characterising drug effects on distinct forms of motivated behaviour that may go unnoticed using conventional assays.