Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice
| Autor: | Vyacheslav N Azev, Ekaterina V. Vasileva, Oleg Yurievich Sokolov, Nikolai F. Myasoedov, Valery M. Lipkin, Yurii A. Zolotarev, Alexander K. Dadayan, N. V. Kost, Evgenii A Kondrakhin, Margarita E Voevodina, A. P. Bogachuk, Georgii I Kovalev |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Elevated plus maze medicine.drug_class Prefrontal Cortex Anxiety Pharmacology Hippocampus Receptors N-Methyl-D-Aspartate Anxiolytic Open field BALB/c Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Receptor Serotonin 5-HT2A Pharmacology (medical) Maze Learning Receptor 5-HT receptor Mice Inbred BALB C Diazepam Dose-Response Relationship Drug biology Chemistry GABAA receptor Brain biology.organism_classification Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health 030104 developmental biology Anti-Anxiety Agents NMDA receptor Oligopeptides 030217 neurology & neurosurgery |
| Zdroj: | Journal of Psychopharmacology. 30:922-935 |
| ISSN: | 1461-7285 0269-8811 |
| DOI: | 10.1177/0269881116660705 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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