Early Attachment Disruption Increases Central Sensitivity of Depressive-Like Behavior to Stimulation by PGE-2

Abstract

Early disruption of filial attachment appears to sensitize underlying threat-related processes to produce vulnerability for developing depression when encountering stressors later in life. Evidence indicates neuroinflammatory signaling mediates this effect, though exact mechanisms are poorly understood. In a guinea pig model, early periods of isolation from the mother produce depressive-like behavior and fever, which sensitize with repeated isolation. Because cyclooxygenase inhibitors reduce these effects, the sensitization appears to involve prostaglandins such as PGE-2. We asked if isolation increased central sensitivity to PGE-2, which could underlie the sensitization process. Experiment 1 established that intraventricular (ICV) infusion of 1 or 3 µg of PGE-2 increased depressive-like behavior in pups. The 3 µg dose also produced an initial suppression and then a rise in core temperature. In Experiment 2, repeated isolation of pups sensitized depressive-like behavior. Days later (early adolescence), 1 µg of ICV-PGE-2 increased depressive-like behavior in previously isolated guinea pigs, but not in non-previously isolated controls. Core temperature was unaffected. Thus, early isolation from the mother increased sensitivity of depressive-like behavior, but not fever, to PGE-2. Results suggest that increased sensitivity to PGE-2 could play a role in the enhanced vulnerability to depression in adolescents previously exposed to early attachment disruption.