Comparison of corticosterone responses to acute stress in mice following different serial blood collection methods

Background. Accurate evaluation of glucocorticoid concentrations during serial blood collection in rodents is often hampered by the stress response elicited by the procedure itself. The optimal method to minimize stress and impact on animal welfare remains debated.
Methods. Hence, we compared corticosterone concentrations in adult mice serially bled by using the retro-orbital sinus puncture or the tail vein incision methods, either with or without exposure to an acute restraint stress.
Results. Corticosterone concentrations were significantly affected by the sampling method, with higher peaks and sustained hypercortisolemia in mice bled with the retroorbital sinus puncture, pointing to the tail vein incision method as preferable for serial blood collections. Mice bled using the tail vein incision reached similar corticosterone peaks regardless of exposure to acute stress.
Conclusions. Our findings suggest that tail vein incision can be used to evaluate neuroendocrine reactivity without exposing mice to restraint procedures. This would improve animal welfare practices in experimental protocols.