The neuroprotective and antioxidative properties of the new neuroactive peptide cyclo-prolylalanine (DKP-9) were studied on the model of acute cerebral disease (ACD, irreversible bilateral carotid occlusion) in rats. Under the conditions of intranasal administration in the therapeutic mode at the doses 0.02 mg/kg or 0.1 mg/kg peptide DKP-9 has increased rats’ survival rate to 40% or 70% respectively. Increase of the DKP-9 dose to 1 mg/kg reduced the protective effect of it. Peptide DKP-9 has effective decreased the neurological and cognitive deficits in acute period of ACD (4 days) exceeding the reference drug semax (0.1 mg/kg, intranasally in same treatment mode). Under the conditions of open-field test the sedative properties of DKP-9 and also the ability of it to reduce rats’ stress-induced anxious reactions were established. Antioxidative properties of DKP-9 are followed by increase of the reduced glutathione level, normalize of the catalase activity, decrease of the level of lipid peroxidation products as well as increase of the brain neurons’ energy metabolism. The further investigation of mechanism of cyclo-prolylalanine (DKP-9) action on the pathogenic links of ischemic cascade is perspective.
Abstract.The aim of study is to evaluate antidepressant-like activity of the new peptidergic neuroprotector acetyl-(D-Lys) -Lys-Arg-Arg-amide, homologous of ACTH 15-18 primary amino acids sequence, that demonstrates nootropic and neuroprotective properties.Using Porsolt swimming test (PST) efficacy of tetrapeptide neuroprotector KK-1 at a single dose of 0.02 mg/kg was investigated 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 until the reserpineinduced depression was reproduced. The indices of rats behavior under the conditions of open-field test (OFT) and PST were evaluated. The influence of both drugs on specific reserpine-induced depressions symptoms (hypothermia and blepharoptosis) was also registered. The results were processed statistically.The tetrapeptide neuroprotector KK-1 reduced immobilization time of rats at PST (statistically significant differences compared with control group), exceeding efficacy of reference drug imipramine. Normalizing of locomotor and exploratory activity in the OFT, decreasing indices of rats helplessness behavior in PST by tetrapeptide neuroprotector KK-1 demonstrates its antagonism with depressive action of reserpine. The tetrapeptide KK-1 showed antidepressant-like action both in intact rats and in rats with the model of reserpineinduced depression. It reduced specific symptoms of depression -hypothermia and blepharoptosis, exceeding the activity of reference drug imipramine.
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