Omega-3 polyunsaturated fatty acids when administered to lactating rats modify the development of experimental anxiety-depressive state in the rat pups exposed to the dipeptidyl peptidase-IV inhibitor diprotin A on the second - third weeks after the birth.

Abstract

Omega-3 polyunsaturated fatty acids (PUFAs) belong to the hypolipidemic drugs, exhibit antioxidant properties and are used in the clinic for secondary prevention of several diseases. The effects of omega-3 PUFAs on the course of the stress-induced and endogenous depression are under investigation. We have previously demonstrated that synthetic inhibitors of prolyl endopeptidase (PEP; EC 3.4.21.26) exhibit antidepressant-like properties in different experimental models of emotional and motivational disorders. It is known that omega-3 PUFAs show PEP inhibitory activity. The purpose of this work was to study the effects of the drug Omacor (Abbot, Germany) containing omega-3 PUFAs, when administered to the lactating Wistar rats, on the emotional and motivational behavior of the offspring with the experimental anxiety-depressive disorder caused by the inhibitor of dipeptidyl peptidase IV (DPP- IV; CD 26; EC 3.4.14.5) diprotin A on postnatal day (PND) 5-18 (second - third weeks of postnatal development).

Methods: We used conventional methods of assessing the emotional and motivational behavior and sensorimotor reactivity in animals. Omega-3 PUFAs were administered to lactating rats at a dose 0.3 g / kg, per os, for 28 days starting from the next day after the birthing. Diprotin A was administered systemically at a dose of 2 mg/kg.

Results: Omega-3 PUFAs when administered to the lactating females, prevented the development of depressive-like behavior in adolescent rats neonatally exposed to DPP-IV inhibitor diprotin A, and contributed to the formation of antidepressive phenotype in control rats. However, under these circumstances, the omega-3 PUFAs increased anxiety and did not prevent an increase in aggression in rats with the experimental anxiety-depressive disorder and increased anxiety and stress-provoked aggression in the controls.

Conclusion: The results support the hypothesis on the involvement of proline-specific peptidases DPP-IV and PEP in the mechanisms of emotional and motivational disturbances and expand the spectrum of omega-3 PUFAs action.