Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice.

Journal of psychopharmacology (Oxford, England)

PubMedID: 27464742

Zolotarev YA, Kovalev GI, Kost NV, Voevodina ME, Sokolov OY, Dadayan AK, Kondrakhin EA, Vasileva EV, Bogachuk AP, Azev VN, Lipkin VM, Myasoedov NF. Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice. J Psychopharmacol (Oxford). 2016;.
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.