The neonatal effect of dipeptidyl peptidase-IV inhibitor diprotin А disrupts sensorimotor reactivity and short-term habituation in adult rats

Abstract

Introduction. Impaired function of dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) is associated with the development of anxiety, affective, and cognitive disorders in mammals. We have previously shown that action of DPP-IV inhibitors of various chemical structures, when administered in the neonatal period, causes anxiety-depressive-like disorders and impaired learning in the conditioned active avoidance reflex test in adult rats. A psychotic component in behavior may develop in conjunction with such violations. Nevertheless, no information is currently available regarding this component in rats in a model of anxiety-depressive-like state induced by rat exposure to DPP-IV inhibitors in the early postnatal period. Learning impairments in this model have not been adequately studied. The evaluation of the startle response to an acoustic stimulus—changing in its amplitude, the sensorimotor gate, and short-term habituation to the action of repeated stimuli, reflecting the process of non-associative learning—is a useful tool for researching these neurophysiological traits.

The aim of the study was to assess sensorimotor reactivity and habituation in adult rats exposed to the neonatal action of the DPP-IV inhibitor diprotin A based on the acoustic startle response (ASR), as well as motor activity, anxiety level, and severity of depressive-like behavior.

Methods. On postnatal days 5–18, rat pups received intraperitoneal injections of either saline or diprotin A (2 mg/kg). Acoustic startle reflex parameters (ASR amplitude and latency), sensorimotor gate based on prepulse inhibition (PPI) magnitude, locomotor and exploratory activity in the open field test, anxiety level in the elevated plus maze test, depressive-like behavior in the forced swim test, and habituation to a repeated overthreshold acoustic stimulus were all evaluated in rats at two months of age.

Results: The time of passive swimming increased in two-month-old adult rats exposed to neonatal diprotin A, indicating depressive-like behavior. These rats showed reduced PPI, diminished short-term habituation, and lower exploratory activity. ASR amplitude, latency, and anxiety levels did not differ from those of the control group.

Conclusion. The findings show that adult rats subjected to neonatal exposure to the DPP-IV inhibitor diprotin A developed a psychotic component in their behavior and had impaired non-associative learning.