Behavioural effects of antidepressants are dependent and independent on the integrity of the dentate gyrus

The dentate gyrus (DG), a part of the hippocampal formation, is a candidate target of antidepressants and may play a role in the development of depressive syndrome; however, there is no direct neurobiological evidence supporting this theory. Here, we examined whether DG integrity is necessary for the behavioural effects of acute or chronic antidepressant treatment. Microinjection of colchicine into DG severely damaged the granule cells, as confirmed by morphological, electrophysiological, and behavioural analyses. Acute treatment with desipramine and fluoxetine decreased the immobility of saline-treated rats in the forced swimming test, whereas this decrease was inhibited in colchicine-treated rats. Chronic treatment with desipramine and fluoxetine also decreased the immobility of saline-treated rats; however, the extensive DG damage induced by colchicine had no effect on this decrease. In the novelty-suppressed feeding test, chronic treatment with desipramine and fluoxetine decreased the latency to feed in saline-treated rats while, once again, the extensive DG damage caused by colchicine had no effect on this decrease. Thus, we concluded that DG integrity was required for the behavioural effects of acute but not chronic antidepressant treatment; this disparity was not due to the time interval between surgery and behavioural tests. These findings indicate that treatment duration determines the influence of DG integrity on antidepressant effects.