Previous studies demonstrated emotional and motivational differences in males and females adult rats subjected to the neonatal administration (5–18 postnatal days) of irreversible synthetic inhibitor of dipeptidyl peptidase IV (DP-IV, EC 3.4.14.5) methionyl-2(S)-cyanopyrrolidine (1 mg/kg). Males and females with anxiety-depressive state showed the difference in the dynamics of proline-specific peptidase activities – DP-IV and prolyl endopeptidase (PEP, EC 3.4.21.26) in brain structures involved in learning and memory that is, in frontal cortex and hippocampus. In rat models of experimental retrograde amnesia, PEP activities were increased in frontal cortex and hippocampus. The purpose of the present study was to investigate learning capability and memory in rats with anxiety-depressive state induced by neonatal administration of DP-IV inhibitor using a twoway active avoidance learning procedure in a shuttle box (one training session of 100 trials; a footshock as an unconditioned stimulus, 0.5 mA, 8 s; combined auditory and light signals as a conditioned stimulus, 10 s). As compared with control, experimental males showed the tendency to worse data acquisition and better memory retention 24 hours after learning session while females demonstrated worse data acquisition and memory retention 2 months after learning session. These data indicate that neonatal administration of DP-IV inhibitor in rats impairs normal functioning of neural circuits of learning and memory in males and females with emotional behavior deficits which may be related to alterations in activities of proline-specific peptidases in brain structures.
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