Anxiolytic activity of BDNF and NT-3 dipeptide mimetics in the elevated plus maze test in mice
| Parent neurotrophin | Code | Neurotrophin loop | Threshold dose (mg/kg, ip) | Activation of post-receptor signaling cascades | Increase in the time spent in open arms compared to the control group (times) | ||
|---|---|---|---|---|---|---|---|
| PI3K/Akt | MAPK/ERK | PLC-γ1 | |||||
| BDNF | GSB-106 [75] | 4 | 1.0 | + | ++ | ++ | 6.2 |
| GSB-214 [75] | 1 | Not active | + | ns | ++ | ns | |
| GTS-201 [75] | 2 | 1.0 | ns | + | ++ | 3.6 | |
| NT-3 | GTS-301 | 4 | Not active | ns | ++ | ++ | ns |
| GTS-302 [43] | 1.0 | ++ | ++ | + | 1.9 | ||
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; 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 increase in the time spent in open arms compared to the control group are presented as means. The reference drug Diazepam (1.0 mg/kg, ip) increased the time spent in open arms under the same conditions by 3.2 times