AbstractThis study aims to identify a panel of blood-cell neuroplasticity-related genes expressed following environmental enrichment stimulation (EE). The Drug detection (DD) training course was an excellent model for the study of EE in the working dog. This research is divided into two experimental trials. In the First Trial, we identified a panel of blood-cell neuroplasticity related-genes associated with DD ability acquired during the training course. In the Second Trial, we assessed the EE additional factor complementary feeding effect on blood-cell neuroplasticity gene expressions. In the First and Second Trials, at different time points of the DD test, blood samples were collected, and NGF, BDNF, VEGFA, IGF1, EGR1, NGFR, and ICE2 blood-cell neuroplasticity related-genes were analyzed. As noted in the First Trial, the DD test in working dogs induced the transient up-regulation of VEGFA, NGF, NGFR, BDNF, and IGF, immediately after the DD test, suggesting the existence of gene regulations. On the contrary, the Second Trial, with feeding implementation, showed an absence of mRNA up-regulation after the DD test. We suppose that complementary feeding alters the systemic metabolism, which, in turn, changes neuroplasticity-related gene blood-cell mRNA. These findings suggested that, in working dogs, there is a cross-talk between blood-cell neuroplasticity-related genes and environmental enrichment. These outcomes could be used to improve future treatments in sensory implementation.