Biology subjects

Xeni, F.

Publications and source records attributed to Xeni, F..

3 recordsLinked to original sources

bioRxiv2026

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

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.

neuroscience↗

bioRxiv2025

Conditioned versus innate effort-based tasks reveal divergence in antidepressant effect on motivational state in male mice

Antidepressant-induced apathy syndrome is reported in a high number of patients. It is characterised by loss of motivation for daily activities and emotional blunting. It has a negative impact on quality of life and treatment outcome, yet the changes in underlying neurobiology driving this syndrome remain unclear. To begin to address this, a comprehensive understanding of how different classes of antidepressant treatment impact on behaviours relevant to apathy is critical. Rodent motivation for reward is commonly assessed using effort-based operant conditioning paradigms such as the Effort for Reward task. However, motivation to perform spontaneous/innate behaviours may provide additional insight into changes in behaviour reflective of daily activities. We tested the acute and chronic effects of antidepressants on the Effort for Reward task, and the spontaneous/innate Effort Based Forage task. Acute treatment revealed important divergence in drug effect between tasks, where selective serotonin reuptake inhibitor (SSRI)/serotonin and noradrenaline reuptake inhibitor (SNRI) treatment impaired foraging behaviour in the Effort Based Forage task, but enhanced high effort, high value reward responding in the Effort for Reward task. Treatment with a noradrenaline reuptake inhibitor (NRI) or multimodal agent impaired foraging behaviour but did not affect high reward responding in the Effort for Reward task. Conversely, chronic treatment with an SSRI but not SNRI enhanced motivated foraging behaviour but led to a general impairment in Effort for Reward task output. Together, these data demonstrate that SSRI treatment induces opposing effects on conditioned versus innate motivation which may have significant translational relevance when interpreting drug effect.

pharmacology and toxicology↗

bioRxiv2023

Validation of a non-appetitive effort-based foraging task as a measure of motivational state in male mice

Motivational disorders such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated or self-driven behaviour. Animals monitored in more naturalistic environments may display more ethologically-relevant behaviours of greater translational value. Here, we aimed to validate a novel, non-appetitive effort-based foraging task as a measure of motivational state in mice. In this task, the mouse can freely choose to exert effort to forage bedding material and shuttle it back to a safe and enclosed environment. The amount of bedding material foraged is used as a readout of motivational state. Acute dopaminergic modulation with haloperidol, amphetamine and methylphenidate, and two phenotypic models known to induce motivational deficits (healthy ageing and chronic administration of corticosterone) were used to validate this task. Consistent with other effort-based decision-making tasks we find that foraging behaviour is sensitive to acute modulation of dopaminergic transmission. We find that both phenotypic models induce differing deficits in various aspects of foraging behaviour suggesting that the task may be used to parse different behavioural profiles from distinct disease phenotypes. Thus, without requiring extended training periods or physiological deprivation, this task may represent a refined and translational preclinical measure of motivation.

pharmacology and toxicology↗