Effect of imipramine and prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on activity of proline-specific peptidases in the brain of rats with experimental anxious-depressive syndrome.
Activities of prolyl endopeptidase and dipeptidyl peptidase IV in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus were measured in rats with the experimental anxious-depressive syndrome induced by treatment with a dipeptidyl peptidase IV inhibitor during the early postnatal period (days 5-18). Prolyl endopeptidase activity was elevated in the frontal cortex, hypothalamus, and nucleus accumbens. Increased activity of dipeptidyl peptidase IV was observed in the hypothalamus and striatum. Norepinephrine/serotonin reuptake inhibitor, imipramine, and noncompetitive prolyl endopeptidase inhibitor, benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, were shown to abolish depression-like behavior of animals in the forced swimming test. These compounds had a normalizing effect on activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats.
Laboratory for General Pathology of Nervous System, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia. nanikh@yandex.ru
N N
NN
Khlebnikova
N A
NA
Krupina
E Yu
EY
Kushnareva
N N
NN
Zolotov
G N
GN
Kryzhanovskii
D000818:Animals; D000831:Animals, Newborn; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000378:metabolism*; D013550:Swimming
D000929:Antidepressive Agents, Tricyclic; D011480:Protease Inhibitors; D011759:Pyrrolidines; C543067:benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine; D008715:Methionine; D018819:Dipeptidyl Peptidase 4; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D007099:Imipramine