Early life stress can increase susceptibility for later development of depressive illness though a process thought to involve inflammatory mediators. Isolated guinea pig pups exhibit a passive, depressive-like behavioral response and fever that appear mediated by proinflammatory activity, and which sensitize with repeated separations. Treatment with an anti-inflammatory can attenuate the behavioral response during the initial separation and separation the following day. Here we used the cyclooxygenase inhibitor naproxen to examine the role of prostaglandins in mediating the depressive-like behavior and core body temperature of young guinea pigs during an initial separation, separation the next day, and separation 10 days after the first. The passive, depressive-like behavior as well as fever sensitized with repeated separation. Three days of injection with 14 mg/kg of naproxen prior to the initial separation reduced depressive-like behavior during all three separations. A 28 mg/kg dose of naproxen, however, had minimal effect on behavior. Fever during the early separations was moderated by naproxen, but only at the higher dose. These results suggest a role of prostaglandins in the behavioral and febrile response to maternal separation, and particularly in the sensitization of depressive-like behavior following repeated separation.

During isolation in a novel environment, guinea pig pups gradually begin to display passive behavior that appears to be mediated by proinflammatory activity, i.e., “sickness behavior”. Administration of substances that increase proinflammatory activity [corticotropin-releasing factor (CRF), lipopolysacchride (LPS)] prior to isolation induces passive behavior from the beginning of the isolation episode. Here we show that reunion with the mother in the novel environment rapidly and potently suppresses the passive behavior of isolated pups (Experiment 1); inhibits the passive behavior of pups administered CRF (10 μg, subcutaneous; Experiment 2); and inhibits the passive behavior of male, though not female, pups administered LPS (250 μg/kg, intraperitoneal; Experiment 3). Together these findings suggest that the presence of the mother either recruits other processes that moderate the impact of proinflammatory processes on brain mechanisms mediating the passive response or initiates compensatory mechanisms that counter the effect of proinflammatory activity. Further, the results suggest that for physically ill animals of social species, the adaptive advantage that accrues from maintaining normal social interactions may sometimes outweigh the advantage gained by engaging in sickness behavior.