Perinatal glucocorticoids disrupt learning: A sexually dimorphic response

Glucocorticoid hormones administered during the perinatal period transiently inhibit postnatal granule cell neurogenesis, and thus interfere with normal hippocampal-dentate gyrus development. Chronic deficits on behavioral tests sensitive to hippocampal-dentate function result from such treatments. In the present study rats of both sexes received either a high dose (100 mg/kg) or low dose (1 mg/kg) of dexamethasone (a synthetic glucocorticoid) on postnatal day four. Control subjects received saline or nutritional deprivation intended to produce body and brain growth suppression comparable to that observed in low dose subjects. Behavioral tests sensitive to cerebellar (motor coordination) and hippocampal (place response acquisition and reversals) dysfunction were conducted in adulthood. Control and nutritional control subjects did not differ from each other on any behavioral measures. Motor coordination tests revealed no evidence of chronic dysfunction in dexamethasone treated or nutritionally deprived subjects. Spatial learning and reversal tests revealed a gender and dose-response effect for dexamethasone treatment. Low dose subjects were impaired relative to controls. High dose subjects exhibited significant learning impairments relative to low dose and saline or nutritional control subjects. Within the high dose group only, female subjects were more impaired than male subjects. These gender dependent effects may be related to enhanced glucocorticoid binding in the hippocampi of female versus male rats.