Priority Communication| Volume 70, ISSUE 5, P434-440, September 01, 2011

Nonsteroidal Anti-Inflammatory Treatment Prevents Delayed Effects of Early Life Stress in Rats

  • Heather C. Brenhouse
    Address correspondence to Heather C. Brenhouse, Ph.D., McLean Hospital, Mail Stop 333, 115 Mill Street, Belmont, MA 02478
    Laboratory for Developmental Neuropharmacology, McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
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  • Susan L. Andersen
    Laboratory for Developmental Neuropharmacology, McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
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      Early developmental insults can cause dysfunction within parvalbumin (PVB)-containing interneurons in the prefrontal cortex. The neuropsychiatric disorders associated with such dysfunction might involve neuroinflammatory processes. Cyclooxygenase-2 (COX-2) is a key mediator of inflammation and is therefore a potential target for preventive treatment. Here, we investigated whether the developmental trajectories of PVB expression and COX-2 induction in the prelimbic region of the prefrontal cortex are altered after maternal separation stress in male rats.


      Male rat pups were separated from their mother and littermates for 4 hours/day between postnatal Days 2 and 20. Western blotting and immunohistochemistry were used to analyze PVB and COX-2 expression in the prefrontal cortex and hippocampus. A separate cohort of animals was treated with a COX-2 inhibitor during preadolescence and analyzed for PVB, COX-2, and working memory performance.


      We demonstrate that maternal separation causes a reduction of PVB and an increase in COX-2 expression in the prefrontal cortex in adolescence, with concurrent working memory deficits. Parvalbumin was not affected earlier in development. Prophylactic COX-2 inhibition preadolescence prevents PVB loss and improves working memory deficits induced by maternal separation.


      These data are the first to show a preventive pharmacological intervention for the delayed effects of early life stress on prefrontal cortex interneurons and working memory. Our results suggest a possible mechanism for the relationship between early life stress and interneuron dysfunction in adolescence.

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