Research reportInvestigations on GSK-3β/NF-kB signaling in stress and stress adaptive behavior in electric foot shock subjected mice

- Study aimed to explore GSK-3β/NF-kB signaling in foot shock induced stress adaptation.
- Acute stress produced behavioral deficits, decreased p-GSK-3β-S9 & increased NF-kB.
- Repeated foot shock stress restored behavioral changes, p-GSK-3β-S9 & NF-kB levels.
- AR-A014418 & DDTC normalized acute stress-induced behavioral and biochemical changes.
- GSK-3β/NF-kB signaling may possibly contribute in stress adaptive behavior.

The present study was designed to explore the role of GSK-3β and NF-kB signaling in electric foot shock-induced stress and stress adaptation. Mice were subjected to foot shocks of 0.5 mA intensity and 1s duration of 1 h to produce acute stress. Animals were exposed to the same stressor for 5 days to induce stress adaptation. The behavioral alterations were assessed using the actophotometer, hole board, open field and social interaction tests. The serum corticosterone levels were assessed as a marker of the HPA axis. The levels of total GSK-3β, p-GSK-3β-S9 and p-NF-kB were determined in the hippocampus, frontal cortex and amygdala. Acute electric foot shock stress produced behavioral and biochemical changes; decreased the levels of p-GSK-3β-S9, produced no change in total GSK-3β levels and increased p-NF-kB levels in the brain. However, repeated exposure of foot shock stress restored the behavioral and biochemical changes along with normalization of p-GSK-3β-S9 and p-NF-kB levels. Administration of AR-A01, a selective GSK-3β inhibitor, or diethyldithiocarbamic acid (DDTC), a selective NF-kB inhibitor, diminished acute stress-induced behavioral and biochemical changes. Furthermore, AR-A014418 normalized acute stress-induced alterations in p-GSK-3β-S9 and p-NF-kB levels, however, DDTC selectively restored NF-kB levels without any change in p-GSK-3β-S9 levels. It probably suggests that NF-kB is a downstream mediator of the GSK-3 signaling cascade. It may conclude that acute stress associated decrease in p-GSK-3β-S9 and increase in p-NF-kB levels in the brain contribute in the development of behavioral and biochemical alterations and normalization of GSK-3β/NF-kB signaling may contribute in stress adaptive behavior in response to repeated electric foot shock-subjected mice.