title: Etazolate, a phosphodiesterase 4 inhibitor reverses chronic unpredictable mild stress-induced depression-like behavior and brain oxidative damage.
abstract: Etazolate, a pyrazolopyridine class compound is selective inhibitor of type 4 phosphodiesterase (PDE4). Previous study in our laboratory has demonstrated that etazolate produced antidepressant-like effect in rodent models of behavioral despair. The present study was designed to investigate whether etazolate could affect the chronic unpredictable mild stress (CUMS)-induced depression in mice. The effect of etazolate on CUMS-induced depression was examined by measuring behavioral parameters and oxidant/antioxidant status of brain tissue. Mice were subjected to different stress paradigms daily for a period of 28days to induce depressive-like behavior. The results showed that CUMS caused depression-like behavior in mice, as indicated by significant (p<0.05) decrease in sucrose consumption and increase in duration of immobility. Moreover, CUMS also significantly (p<0.05) increased the oxidative stress markers and decreased the antioxidant enzymes activity. Chronic administration of etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) significantly (p<0.05) inhibited the CUMS-induced behavioral (decreased sucrose consumption and increased duration of immobility) and biochemical (increased lipid peroxidation and nitrite level; decreased glutathione, superoxide dismutase and catalase activity) changes. No alteration was observed in locomotor activity. Additionally, in the present study, the efficacy of etazolate (1mg/kg., p.o.) on the behavioral and biochemical paradigms was found comparable to that of fluoxetine, used as standard antidepressant. In conclusion, the results of the present study suggested that etazolate alleviated the CUMS-induced depression in mice, which is at least in part mediated by modulating oxidative-nitrosative stress status in mice brain.
authors: Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. kumarjindal26@gmail.com
authors: Ankur
authors: A
authors: Jindal
authors: Radhakrishnan
authors: R
authors: Mahesh
authors: Shvetank
authors: S
authors: Bhatt
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002908:Chronic Disease; D004974:Etazolate / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000517:prevention & control*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D010726:Phosphodiesterase Inhibitors; D005473:Fluoxetine; D004974:Etazolate