Assessment of social behavior in rats exposed to sick partners and its relation to central cytokine expression

Abstract

Acute illness not only reduces the expression of social behavior by sick rodents, but also leads to avoidance responses when detected by healthy, would-be social partners. This raises the intriguing question of whether exposure to a sick conspecific might elicit an anticipatory immune response in healthy conspecifics to facilitate defense against future infection. Group- or isolate-housed adult male Sprague–Dawley rats (N = 64) were examined for social behavior directed toward a sick conspecific. A 30 min social interaction test occurred 3 h following injection with LPS (250 μg/kg), after which brains were harvested for cytokine assessments. As expected: (i) there was a robust suppression of social interaction directed against sick conspecifics; and (ii) isolate-housing increased the expression of socially-directed behavior. Within socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and PVN) from LPS-injected rats, there was a robust increase in IL-1, IL-6 and TNF-alpha across all sites. When brains of healthy subjects were examined, only a modest increase in TNF-alpha in the olfactory bulb of rats exposed to sick conspecifics was observed, providing little evidence for an anticipatory cytokine response in rats exposed to sick conspecifics. These data replicate and extend our prior work showing that healthy rats strongly avoid sick conspecifics, and provide new evidence to suggest that recent housing history (relative to 5 days of isolation) potently modulates cytokine responses evoked by LPS.