To blink or not to blink, that is the question: Reassessing rabbit eyeblink conditioning for learning and memory evaluation in nonclinical safety studies.

Eyeblink conditioning (EBC) has been explored as a cognitive endpoint in rabbit pre- and postnatal development (PPND) and juvenile toxicity (JAS) studies; however, species-specific behavioral constraints, procedural demands, and the basic nature of the task may limit its ability to address complex neurobehavioral objectives in regulatory contexts. While EBC provides a measure of associative learning, it may lack the sensitivity and relevance required for regulatory toxicology studies designed to evaluate human health risk through complex neurobehavioral assessment paradigms. In addition, given the procedural variability and the sensitivity of the rabbit model, the reliability of the resulting data should be carefully considered. Although rabbits are increasingly considered as an alternative nonrodent species due to ethical and logistical constraints associated with nonhuman primates, their behavioral repertoire restricts the applicability of traditional rodent-based neurobehavioral assessments. Therefore, more practical and species-adapted approaches, such as a rabbit-specific Functional Observational Battery (FOB), would provide a more appropriate and scientifically meaningful assessment of neurodevelopmental status in this species, while aligning testing objectives with animal welfare principles.