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Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.
Neurochem Int. 2013 Nov; 63(5):465-75.NI

Abstract

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level.

Authors+Show Affiliations

Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: kumarjindal26@gmail.com.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23974048

Citation

Jindal, Ankur, et al. "Etazolate Rescues Behavioral Deficits in Chronic Unpredictable Mild Stress Model: Modulation of Hypothalamic-pituitary-adrenal Axis Activity and Brain-derived Neurotrophic Factor Level." Neurochemistry International, vol. 63, no. 5, 2013, pp. 465-75.
Jindal A, Mahesh R, Bhatt S. Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level. Neurochem Int. 2013;63(5):465-75.
Jindal, A., Mahesh, R., & Bhatt, S. (2013). Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level. Neurochemistry International, 63(5), 465-75. https://doi.org/10.1016/j.neuint.2013.08.005
Jindal A, Mahesh R, Bhatt S. Etazolate Rescues Behavioral Deficits in Chronic Unpredictable Mild Stress Model: Modulation of Hypothalamic-pituitary-adrenal Axis Activity and Brain-derived Neurotrophic Factor Level. Neurochem Int. 2013;63(5):465-75. PubMed PMID: 23974048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level. AU - Jindal,Ankur, AU - Mahesh,Radhakrishnan, AU - Bhatt,Shvetank, Y1 - 2013/08/22/ PY - 2013/03/19/received PY - 2013/07/28/revised PY - 2013/08/15/accepted PY - 2013/8/27/entrez PY - 2013/8/27/pubmed PY - 2014/6/3/medline KW - BDNF KW - CUMS KW - Depression KW - Etazolate KW - HPA axis SP - 465 EP - 75 JF - Neurochemistry international JO - Neurochem. Int. VL - 63 IS - 5 N2 - Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/23974048/Etazolate_rescues_behavioral_deficits_in_chronic_unpredictable_mild_stress_model:_modulation_of_hypothalamic_pituitary_adrenal_axis_activity_and_brain_derived_neurotrophic_factor_level_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(13)00214-3 DB - PRIME DP - Unbound Medicine ER -