Diazepam suppresses aggressive rat behavior in models of anxiety-depressive disorder induced by neonatal exposure to dipeptidyl peptidase IV inhibitors

Abstract

Background. Disorders of the emotional-motivational sphere are a serious challenge the modern society is facing. Aversive events in early ontogenesis may underlie development of affective disorders, pathological anxiety, and increased aggression. Validated models of these diseases could be useful in translational research for studying the pathophysiology of mental disorders. The study aim was evaluating the predictive validity of models for the anxiety-depressive condition with increased aggressiveness induced by neonatal exposure to the dipeptidyl peptidase-IV inhibitors, diprotin A and sitagliptin. To this aim, the study focused on effects of the benzodiazepine tranquilizer, diazepam, that is used in clinic for the treatment of aggressiveness symptoms.
Materials and methods. Diprotin A (2 mg/kg) or sitagliptin (4 mg/kg) was administered to rat pups on postnatal days 5-19, intraperitoneally; control animals received saline. Aggressive behavior was evaluated using the Social Contact test in twomonth-old rats twice with a daily interval; first, against the background of saline and then against the background of diazepam (1.25 mg/kg, i.p.) administered 30 minutes prior to the test.
Results. In both models, diazepam similarly alleviated manifestations of stress-induced aggression in adult animals by decreasing the number of and the time spent in aggressive contacts and increasing the time spent in non-aggressive contacts.

Conclusion. Suppression of aggressive behavior by diazepam confirms compliance of the developed models for emotionalmotivational disorders associated with increased aggression induced by the neonatal exposure to dipeptidyl peptidase-IV inhibitors with the criterion of predictive validity.