Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine.

Long-term adrenalectomy (ADX) causes a nearly complete and selective loss of granule cells in the dentate gyrus (DG) of the hippocampus. Previously, learning and memory deficits have been observed following ADX-induced granule cell degeneration for tasks that require the hippocampus. Our objective here was to determine whether corticosterone (CORT) replacement and treatment with the neurogenic compound fluoxetine could reverse behavioral deficits after ADX. We trained ADX and control rats in a moving, hidden platform version of the Morris water task before chronic administration (6 weeks) of CORT and either fluoxetine or vehicle. After treatment, all rats were retested in the Morris water task. Brains were labeled for the endogenous neurogenic markers Ki67 and doublecortin. Here we provide evidence that neurogenesis persists at a normal rate in the hippocampus after long-term ADX. After 8 weeks of CORT and fluoxetine administration, ADX-fluoxetine rats did not differ significantly compared to ADX-vehicle rats receiving CORT or compared to control rats in the number of Ki67 or doublecortin labeled cells. ADX-fluoxetine rats also did not significantly differ from ADX-vehicle rats in regards to granule cell layer thickness. Our results indicate that long-term ADX is associated with impaired spatial ability in the Morris water task and that neither chronic treatment with CORT, nor with CORT and fluoxetine are capable of altering the Morris water task deficit.