Prevention of chronic stress-induced depression-like behavior by inducible nitric oxide inhibitor

Depression is associated with significant morbidity and functional disability, and it is thus important to reveal the mechanism of depression. A variety of studies suggest an involvement of neuronal nitric oxide synthase in the pathophysiological mechanism of none-stress-associated depression-like behavior in rodents. It is unknown, however, whether inducible nitric oxide synthase (NOS) also makes contributions to the mechanism of depression. Here we show that intra-hippocampal injections of the NOS inhibitor aminoguanidine during chronic unexpected mild stress (CUMS) suppressed CUMS-induced depression-like behavioral changes, including a reduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test. Thus, inhibition of hippocampal NOS may prevent the development of CUMS model of depression. (c) 2008 Elsevier Ireland Ltd. All rights reserved.