DENTATE GYRUS DESTRUCTION AND SPATIAL-LEARNING IMPAIRMENT AFTER CORTICOSTEROID REMOVAL IN YOUNG AND MIDDLE-AGED RATS

We investigated the functional and behavioral implications of chronic corticosteroid removal in young and middle-aged rats. Prepubertal and 13-month-old rats were adrenalectomized (ADX) or sham operated (SHAM). The young ADX rats were divided further into three groups: ADX with n o hormone replacement, ADX given corticosterone chronically, (chCORT), and ADX given corticosterone acutely at the time of Morris water maze testing (acCORT). All rats were run on the Morris water maze 12 weeks after surgery. They were then sacrificed and the brains were removed for histological analysis. The results showed that prolonged corticost eroid absence caused major damage to the dentate gyrus and learning im pairment on the Morris water maze. The chCORT rats had little dentate gyrus cell loss and were as efficient as the controls in Morris water maze performance, whereas the acCORT rats had dentate gyrus cell loss and were impaired in the spatial acquisition task. Furthermore, exogen ously administered corticosterone had an interactive effect on ADX rat s. Water maze performance was improved in dentate gyrus damaged rats ( acCORT) compared to ADX rats not given corticosterone, whereas ADX rat s with very little dentate gyrus damage (chCORT) did not exhibit bette r water maze performance relative to controls. Middle-aged ADX rats lo st cells only in the dorsal blade of the dentate gyrus but they did no t show a learning impairment in the Morris water maze relative to the middle-aged controls. These results indicate that corticosteroids are trophic for the dentate gyrus, that mature granule cells are less affe cted by adrenalectomy, that corticosteroid absence is responsible for some water maze impairment in ADX rats, but that in addition to cortic osteroid absence, a substantial amount of dentate gyrus damage is nece ssary to impair spatial learning. (C) 1995 Wiley-Liss, Inc.