Premium
Inhibition of Neuronal Nitric Oxide Synthase and Soluble Guanylate Cyclase Prevents Depression‐Like Behaviour in Rats Exposed to Chronic Unpredictable Mild Stress
Author(s) -
Yazir Yusufhan,
Utkan Tijen,
Aricioglu Feyza
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2012.00877.x
Subject(s) - anhedonia , behavioural despair test , nitric oxide , nitric oxide synthase , hippocampus , medicine , endocrinology , depression (economics) , soluble guanylyl cyclase , chemistry , animal models of depression , pharmacology , guanylate cyclase , antidepressant , dopamine , macroeconomics , economics
Depression is the most common psychiatric disorder. It is well established that endogenous nitric oxide ( NO ) contributes to chronic unpredictable mild stress ( CUMS )‐induced depression. The aim of this study was to investigate brain‐derived neurotropic factor ( BDNF ) expression in CUMS ‐induced depression‐like behaviour in rats. Rats were exposed to CUMS for 5 weeks. A specific and selective n NOS inhibitor, 3‐bromo‐7‐nitroindazole (3‐Br‐7‐NI; 20 mg/kg/day, i.p.), and a specific soluble guanylate cyclase (s GC ) inhibitor, 1H‐(1,2,4)oxadiazolo(4,3‐a)quinoxalin‐1‐one ( ODQ ; 10 mg/kg/day, i.p.), were administered during CUMS . The forced swimming test ( FST ) was used to assess despair and sucrose consumption, and sucrose preference test was used to assess anhedonia that are the main symptoms of the depression. We show that both 3‐Br‐7‐NI and ODQ administration during CUMS suppressed CUMS ‐induced, depression‐like behavioural changes, including reduced sucrose preference, body‐weight and locomotor activity as well as increased immobility time in the FST . CUMS also significantly decreased BDNF protein levels in the CA 1 and CA 3 regions of the hippocampus, which was reversed by 3‐Br‐7‐NI and ODQ administration. Our findings suggest a novel role for n NOS and s GC ‐c GMP in the development of the CUMS model of depression.