Effects of several degrees of chronic social defeat stress on emotional and spatial memory in CD1 mice

Early-life adverse experiences (first hit) lead to coping strategies that may confer resilience or vulnerability to later experienced stressful events (second hit) and the subsequent development of stress-related psychopathologies. Here, we investigated whether exposure to two stressors at different stages in life has long-term effects on emotional and cognitive capabilities, and whether the interaction between the two stressors influences stress resilience. Male rats were subjected to social defeat stress (SDS, first hit) in adolescence and to a single episode of prolonged stress (SPS, second hit) in adulthood. Behavioral outcomes, hippocampal expression of brain-derived neurotrophic factor, and plasma corticosterone levels were tested in adulthood. Rats exposed to both stressors exhibited resilience against the development of stress-induced alterations in emotional behaviors and spatial memory, but vulnerability to cued fear memory dysfunction. Rats subjected to both stressors demonstrated resilience against the SDS-induced alterations in hippocampal brain-derived neurotrophic factor expression and plasma corticosterone levels. SPS alone altered locomotion and spatial memory retention; these effects were absent in SDS-exposed rats later exposed to SPS. Our findings reveal that exposure to social stress during early adolescence influences the ability to cope with a second challenge experienced later in life.

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Brain histamine and oleoylethanolamide restore behavioral deficits induced by chronic social defeat stress in mice

Neurobiology of Stress ◽

10.1016/j.ynstr.2021.100317 ◽

2021 ◽

pp. 100317

Author(s):

Barbara Rani ◽

Andrea Santangelo ◽

Adele Romano ◽

Justyna Barbara Koczwara ◽

Marzia Friuli ◽

...

Keyword(s):

Social Defeat ◽

Social Defeat Stress ◽

Behavioral Deficits ◽

Brain Histamine ◽

Chronic Social Defeat Stress

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Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

Biomolecules ◽

10.3390/biom11020252 ◽

2021 ◽

Vol 11 (2) ◽

pp. 252

Author(s):

Tatiana A. Gudasheva ◽

Anna V. Tallerova ◽

Armen G. Mezhlumyan ◽

Tatyana A. Antipova ◽

Ilya O. Logvinov ◽

...

Keyword(s):

Dose Range ◽

Social Defeat ◽

Social Defeat Stress ◽

In Vivo Experiments ◽

Trk Receptor ◽

Chronic Social Defeat Stress ◽

Swimming Test ◽

Scientific Group

A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1–5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling.

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