title: Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice.
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.
authors.affiliation: Institute of Molecular Genetics of RAS, Moscow, Russia zolya@img.ras.ru.
authors.forename: Yurii A
authors.initials: YA
authors.lastname: Zolotarev
authors.affiliation: Zakusov Research Institute of Pharmacology, Moscow, Russia.
authors.forename: Georgii I
authors.initials: GI
authors.lastname: Kovalev
authors.affiliation: Mental Health Research Centre, Moscow, Russia.
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Kost
authors.affiliation: Mental Health Research Centre, Moscow, Russia.
authors.forename: Margarita E
authors.initials: ME
authors.lastname: Voevodina
authors.affiliation: Mental Health Research Centre, Moscow, Russia.
authors.forename: Oleg Y
authors.initials: OY
authors.lastname: Sokolov
authors.affiliation: Institute of Molecular Genetics of RAS, Moscow, Russia.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Dadayan
authors.affiliation: Zakusov Research Institute of Pharmacology, Moscow, Russia.
authors.forename: Evgenii A
authors.initials: EA
authors.lastname: Kondrakhin
authors.affiliation: Zakusov Research Institute of Pharmacology, Moscow, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Vasileva
authors.affiliation: Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Bogachuk
authors.affiliation: Branch of Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, RAS, Pushchino, Moscow Region, Russia.
authors.forename: Vyacheslav N
authors.initials: VN
authors.lastname: Azev
authors.affiliation: Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Valery M
authors.initials: VM
authors.lastname: Lipkin
authors.affiliation: Institute of Molecular Genetics of RAS, Moscow, Russia.
authors.forename: Nikolai F
authors.initials: NF
authors.lastname: Myasoedov
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D009842:Oligopeptides; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; C513648:threonyl-glycyl-glutamyl-asparaginyl-histidylarginine; D003975:Diazepam
keywords: Anxiolytics; HLDF-6; NMDA receptors; elevated plus maze; open field