Decreased proliferation in the adult rat hippocampus after exposure to the Morris water maze and its reversal by fluoxetine

Granular cell proliferation in the adult hippocampus decreases during aging and after chronic stress, while it can be increased by physical activity or treatment with the antidepressant fluoxetine. We investigated whether the physical and cognitive stimulation accompanied by stress in the commonly used Morris water maze affects the rate of proliferation and whether the induced changes can be influenced by antidepressant treatment with fluoxetine. Proliferating cells in the dentate gyrus were labeled by three injections of BrdU during the 24 h preceding sacrifice. Early differentiation to neuronal progeny was studied by immunohistochemical staining for doublecortin (DCX), a microtubule binding protein expressed in newborn neurons. Acquisition learning in the water maze for 15 days caused a significant decrease in granular cell proliferation in the granular cell layer of the hippocampus. The decrease in the number of BrdU- and DCX-positive cells was reversed to control levels by the use of fluoxetine during the water maze training. Fluoxetine treatment alone increased the number of BrdU-positive cells, but did not increase the number of DCX-positive cells. We conclude that the exposure of adult male rats to water maze acquisition trials is a stressful experience that significantly suppresses the production of new granular cells and that this stressful effect can be blocked by the concomitant administration of the antidepressant fluoxetine.