Non-aversive handling in laboratory animals and its effects on depressive-like and anxiety-related behaviors: A scoping review (2025)

Castro de Jesus, L., S․ Rodrigues, A. L.

Abstract

Stress is an adaptive response to environmental demands, but increased intensity and frequency can lead to impaired adaptive functions. Stress is considered a risk factor for Major Depressive Disorder, a multifactorial disorder that often coexists with anxiety. Picking up laboratory mice by the tail is the most common method for animal capture and may create background stress. Non-aversive handling (NAH) includes capturing the animal with the help of a tunnel or by capturing the animal with cupped hands. Given the importance of stress-induced models in the investigation of depressive-like and anxiety-related behaviors, we conducted a literature review to investigate the current knowledge on the behavioral effects of NAH in laboratory animals. While the ability of NAH to counteract depressive-like behavior has yielded mixed results, its ability to induce anxiolytic-like effects in mice has been confirmed by several studies. Some of the studies also investigated the impact of NAH on stress-related molecules (e.g. corticosterone) and physiological parameters (i.e. adrenal gland mass and body weight). The anxiolytic-like effect elicited by NAH seems to be well established in the literature, but little is known about the biochemical pathways underlying it and its antidepressant potential.