PMID- 25120105 OWN - NLM STAT- MEDLINE DCOM- 20150811 LR - 20211021 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 232 IP - 3 DP - 2015 Feb TI - 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. PG - 623-37 LID - 10.1007/s00213-014-3705-0 [doi] AB - RATIONALE: 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. OBJECTIVES: 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. RESULT: 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. CONCLUSION: 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. FAU - Jindal, Ankur AU - Jindal A AD - Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan, 333031, India, kumarjindal26@gmail.com. FAU - Mahesh, Radhakrishnan AU - Mahesh R FAU - Bhatt, Shvetank AU - Bhatt S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140815 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Antidepressive Agents) RN - 0 (Phosphodiesterase 4 Inhibitors) RN - I89Y79062L (Etazolate) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Behavior, Animal/*drug effects MH - Depression/*drug therapy MH - Etazolate/*pharmacology MH - Hippocampus/*drug effects MH - Male MH - Phosphodiesterase 4 Inhibitors/*pharmacology MH - Rats MH - Rats, Wistar EDAT- 2014/08/15 06:00 MHDA- 2015/08/12 06:00 CRDT- 2014/08/15 06:00 PHST- 2014/04/20 00:00 [received] PHST- 2014/07/21 00:00 [accepted] PHST- 2014/08/15 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/08/12 06:00 [medline] AID - 10.1007/s00213-014-3705-0 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2015 Feb;232(3):623-37. doi: 10.1007/s00213-014-3705-0. Epub 2014 Aug 15.