Machine learning-based model for behavioural analysis in rodents applied to the forced swim test.

Journal: Scientific reports
Published Date:

Abstract

The Forced Swim Test (FST) is a widely used preclinical model for assessing antidepressant efficacy, studying stress response, and evaluating depressive-like behaviours in rodents. Over the last 10 years, more than 5500 scientific articles reporting the use of the FST have been published. Despite its widespread use, the FST behaviours are still manually scored, resulting in a labor-intensive and time-consuming process that is prone to human bias and variability. Despite eliminating some biases, existing automated systems are costly and typically only able to distinguish between immobility and active behaviours. Therefore, they are often unable to accurately differentiate the major subtypes of movement patterns, such as swimming and climbing. To address these limitations, we propose a novel approach based on machine learning (ML) using a three-dimensional residual convolutional neural network (3D RCNN) that processes video pixels directly, capturing the spatiotemporal dynamics of rodent behaviour. Our ML model was validated against manual scoring in rats treated with fluoxetine and desipramine, two antidepressants known to induce distinct behavioural patterns. The ML model successfully differentiated among swimming, climbing, and immobility behaviours, demonstrating its potential as a standardized and unbiased tool for automatized behavioural analysis in the FST. Subsequently, we successfully validated our model by testing its ability to distinguish between drugs that predominantly evoke climbing (i.e., amitriptyline), those that preferentially facilitate swimming (i.e., paroxetine), and those that evoke both in a more balanced manner (i.e., venlafaxine). This approach represents a significant advancement in preclinical research, providing a more accurate and efficient method to analyze forced swimming data in rodents. We anticipate that in addition to the FST, our model and approach could be extended for application to various behavioural tests in laboratory animals, by training with specific datasets.

Authors

  • Andrea Della Valle
    School of Pharmacy, Center of Neuroscience, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, MC, Italy.
  • Sara De Carlo
    School of Pharmacy, Center of Neuroscience, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, MC, Italy.
  • Gregorio Sonsini
    School of Pharmacy, Center of Neuroscience, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, MC, Italy.
  • Sebastiano Pilati
    School of Science and Technology, Physics Division, University of Camerino, Camerino, Italy.
  • Andrea Perali
    School of Pharmacy, Physics Unit, Pharmacology Unit, University of Camerino, Camerino, Italy.
  • Massimo Ubaldi
    School of Pharmacy, Center of Neuroscience, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, MC, Italy.
  • Roberto Ciccocioppo
    School of Pharmacy, Center of Neuroscience, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, MC, Italy. roberto.ciccocioppo@unicam.it.