title: Etazolate, a phosphodiesterase-4 enzyme inhibitor produces antidepressant-like effects by blocking the behavioral, biochemical, neurobiological deficits and histological abnormalities in hippocampus region caused by olfactory bulbectomy.
abstract: BACKGROUND
  Olfactory bulbectomy (OBX) is a widely used model for antidepressant screening and known to induce neurodegeneration in several brain areas. Our earlier studies demonstrated that etazolate produced antidepressant-like effects in behavioral despair models of depression; however, the potential role of etazolate on behavior and morphological changes in the hippocampus region along with its underlying mechanism(s) following OBX has not been adequately addressed.
  
  
  OBJECTIVE
  We evaluated if etazolate could protect against OBX-induced depression-like behavioral deficits and neurodegeneration. The possible underlying mechanism of etazolate in OBX model was also investigated.
  
  
  METHODS
  The effects of etazolate were measured in a battery of behavioral paradigms, including the forced swim test (FST), sucrose consumption, open arm activity in elevated plus maze (EPM), and hyperemotionality tests. The underlying mechanisms were investigated by measuring serum corticosterone (CORT), cyclic adenosine monophosphate (cAMP), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and oxidative/nitrosative stress (lipid peroxidation and nitrite) levels and antioxidant enzymes, like reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in the hippocampus.
  
  
  RESULTS
  OBX rats showed depression-like behavior anomalies in behavioral paradigms. OBX rats also showed high CORT and decreased cAMP, phosphorylated CREB (pCREB), and BDNF levels. Additionally, we found increased oxidative/nitrosative stress and reduced antioxidant enzyme levels in the hippocampus. Histopathological analysis showed morphological changes and neuronal loss in the hippocampus. Etazolate (0.5 and 1 mg/kg) attenuated the OBX-induced behavioral, biochemical, neurobiological, and histopathological alterations.
  
  
  CONCLUSIONS
  The aforesaid results suggest that etazolate produces an antidepressant-like effect and neuroprotection in OBX, which is possibly mediated by modulating biochemical and neurobiological markers in the hippocampus.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, 333031, India, kumarjindal26@gmail.com.
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy*; D004974:Etazolate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000928:Antidepressive Agents; D058988:Phosphodiesterase 4 Inhibitors; D004974:Etazolate