Mapping in mice the brain regions involved in the anxiolytic-like properties of α-casozepine, a tryptic peptide derived from bovine α s1 -casein

α-Casozepine, a bioactive peptide from milk casein, displays an anxiolytic-like activity in many species. Since its mode of action is still not elucidated, a study was conducted in Swiss mice to investigate c-Fos expression, a marker of neuronal activity, in different brain areas. After an intraperitoneal injection of α-casozepine (1 mg/kg), animals were placed either in a non-stressful or in an anxiety-inducing situation triggered with a light/dark box. No effect of α-casozepine on c-Fos expression was observed in the non-stressful situation. In the stressful situation, modulation of neuronal activity by α-casozepine was observed in different brain regions compared to that of vehicle. However, while diazepam, a benzodiazepine, modulated neuronal activity the same way in hippocampus, accumbens nucleus and hypothalamus, differences were observed in c-Fos expression in amygdala and prefrontal cortex compared to α-casozepine. These results strengthen the assumption that the anxiolytic mechanisms of α-casozepine differ partly of those of diazepam.