Antidepressant-like activity of NGF, BDNF and NT-3 dipeptide mimetics in the forced swim test in mice

Parent neurotrophinCodeNeurotrophin loopThreshold dose (mg/kg, ip)Activation of post-receptor signaling cascadesDecrease in immobility time compared to the control group (%)
PI3K/AktMAPK/ERKPLC-γ1Acute administrationSubchronic administration
NGFGK-2 [67]41.0++ns++ns14
GK-6 [67]12.0+++ns15
BDNFGSB-106 [67]41.0+++++2016
GSB-214 [67]11.0+ns++ns20
GTS-201 [67]2Not activens+++nsns
NT-3GTS-301 [33]410.0ns++++ns27
GTS-302 [36, 43]0.5+++++3134

ip: intraperitoneally; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinase; PLC-γ1: phospholipase C-gamma; GK-2: bis-(monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide; GK-6: bis-(N-aminocaproyl-glycyl-L-lysine) hexamethylenediamide; GSB-106: bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide; GSB-214: bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide; GTS-201: bis-(N-hexanoyl-L-seryl-L-lysine) hexamethylenediamide; GTS-301: bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) hexamethylenediamide; GTS-302: bis-(N-gamma-oxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide; +: the effect is inferior to the full-length neurotrophin in terms of intensity and/or duration; ++: the effect is comparable to the full-length neurotrophin in terms of intensity and duration; ns: non-significant. All effects not labeled as “ns” are statistically significant. The data on the reduction in immobility time compared to the control group (%) are presented as means. The reference drug Amitriptyline (10.0 mg/kg, ip) reduced immobility time under the same conditions in various experiments up to 40%