1. Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice.
- Author
-
Zolotarev YA, Kovalev GI, Kost NV, Voevodina ME, Sokolov OY, Dadayan AK, Kondrakhin EA, Vasileva EV, Bogachuk AP, Azev VN, Lipkin VM, and Myasoedov NF
- Subjects
- Animals, Anti-Anxiety Agents administration & dosage, Anxiety physiopathology, Brain drug effects, Brain metabolism, Diazepam pharmacology, Disease Models, Animal, Dose-Response Relationship, Drug, Hippocampus drug effects, Hippocampus metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Oligopeptides administration & dosage, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Receptor, Serotonin, 5-HT2A metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Anti-Anxiety Agents pharmacology, Anxiety drug therapy, Maze Learning drug effects, Oligopeptides pharmacology
- Abstract
This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities. We showed, for the first time, that the peptide HLDF-6-amide has high anxiolytic activity. We used 'open field' and 'elevated plus maze' tests to demonstrate anxiolytic effects of HLDF-6-amide (0.1 and 0.3 mg/kg intranasally), which were comparable to those of the reference drug diazepam (0.5 mg/kg). Five daily equipotent doses of HLDF-6-amide selectively mitigated anxiety and increased the density of NMDA receptors in the hippocampus of stress-susceptible BALB/c mice, and had no effect on stress-resilient C57BL/6 mice. The subchronic administration of HLDF-6-amide showed no effect on the density of GABAA and nicotine receptors but was accompanied by a nonselective decrease of the 5-HT2A serotonin receptor density in frontal cortex of both strains. The mechanism of the specific anxiolytic activity of HLDF-6-amide may include its action on the NMDA-glutamatergic receptor system of the hippocampus and on serotonin 5-HT2A-receptors in the prefrontal cortex. The psychotropic activity of HLDF-6-amide is promising for its introduction to medical practice as a highly effective anxiolytic medicine for mental and neurological diseases., (© The Author(s) 2016.)
- Published
- 2016
- Full Text
- View/download PDF