Sensitization of depressive-like behavior is attenuated by disruption of prostaglandin synthesis days following brief early attachment-figure isolation.

Childhood psychological trauma appears to sensitize stress-related neuroinflammatory systems to increase later vulnerability for depression and other stress-related mental disorders. Isolation of guinea pig pups from the maternal attachment figure for 3 h in threatening surroundings leads to a sensitization of inflammatory-mediated, depressive-like behavior and fever during later isolations. A previous study found the non-selective COX inhibitor naproxen administered before the initial isolation moderated depressive-like behavior and its sensitization. Here, we examined effects of naproxen given following early isolation. Male and female guinea pig pups surgically implanted with telemetry devices to measure core temperature were isolated for 3 h on 2 consecutive days near weaning (first isolation Day 20-24). Several days later, they began 4 consecutive days of injection with either saline vehicle or 10 or 20 mg/kg naproxen prior to a third isolation in early adolescence, that is, 10 days after their first isolation. Across the first two isolations, depressive-like behavior and fever sensitized. Both doses of naproxen attenuated depressive-like behavior during the third isolation. Fever was unaffected. Results suggest prostaglandin mediation of sensitization of depressive-like behavioral, but not febrile, responses to subsequent isolation. Findings also support further study of anti-inflammatory treatments to mitigate lasting consequences of early-attachment disruption.