The antidepressant-like activity of the new tetrapeptide neuroprotector KK-1, homologous of ACTH15-18 sequence (An experimental study)

Abstract

The aim of study is to evaluate antdepressant-like actvity of the new peptdergic neuroprotector acetyl-(D-Lys)-Lys-ArgArg-amide, homologous of ACTH15-18 primary amino acids sequence, that demonstrates nootropic and neuroprotectve propertes. Using Porsolt swimming test (PST) efcacy of tetrapeptde neuroprotector KK-1 at a single dose of 0.02 mg/kg was investgated on 16 white random bred male rats (body mass equaled 180-220 grams). Imipramine (15 mg/kg i.p.) was used as a reference drug. Then depression was induced in these rats by reserpine (4 mg/kg, i.p.). The KK-1 (intranasally, i.n.) and imipramine were administered once a day during 3 days untl the reserpine-induced depression was reproduced. The indices of rats behavior under the conditons of open-feld test (OFT) and PST were evaluated. The influence of both drugs on specifc reserpine-induced depressions symptoms (hypothermia and blepharoptosis) was also registered. The results were processed statstcally. The tetrapeptde neuroprotector KK-1 reduced immobilizaton tme of rats at PST (statstcally signifcant differences compared with control group), exceeding efcacy of reference drug imipramine. Normalizing of locomotor and exploratory actvity in the OFT, decreasing indices of rats helplessness behavior in PST by tetrapeptde neuroprotector KK-1 demonstrates its antagonism with depressive acton of reserpine. The tetrapeptde KK-1 showed antdepressant-like action both in intact rats and in rats with the model of reserpine-induced depression. It reduced specifc symptoms of depression – hypothermia and blepharoptosis, exceeding the actvity of reference drug imipramine.