Chronic foot shock induces hyperactive behaviors and accompanying pro- and anti-inflammatory responses in mice

Behavioral and accompanying physiological and immunological changes were investigated at various times during chronic irregular mild foot shock (CMFS) in adult male BALB/c mice. CMFS induced a significant hyperlocomotor activity in a familiar environment as well as increased consumption of chocolate milk (a favored drink) throughout the 5-week stress period. Unlike other chronic stress models, CMFS did not induce depressive-like behaviors. Hyperactivity was associated with transient elevations of pro-inflammatory cytokines (TNFα and IL-1β) and IL-2 and more sustained (IL-10) or later (arginase activity) elevations in anti-inflammatory mediators in the spleen (serum levels below levels of detection) suggesting a transition from a pro-inflammatory state to an anti-inflammatory state during CMFS. Similar increases in brain levels of IL-2 and arginase activity were also detected and may contribute to CMFS-induced hyperactivity as both of these mediators have been shown to induce hyperactivity. To our knowledge, this is the first time that increased arginase activity has been documented during a stress paradigm. Altogether, the data indicate that CMFS induces behavioral changes distinct from other chronic stress models. CMFS is associated with multiple dynamic immunological changes, suggesting involvement of multiple factors in chronic stress-induced behavioral changes.