title: Protective Effect of Irbesartan an Angiotensin (AT1) Receptor Antagonist in Unpredictable Chronic Mild Stress Induced Depression in Mice.
abstract: Objective:Oxidative stress and alternation of renin-angiotensin system has been implicated in the pathophysiology of various cardio vascular, endocrine including mood and anxiety disorders. The present study evaluated the role of irbesartan in stress induced different models of depression.Materials and method:Mice were treated with irbesartan (40 mg/kg), fluoxetine (25 mg/kg) alone in combination orally. Drugs treatment started after 2 weeks from the beginning of the unpredictable mild stress (UCMS) protocol. Behavioural tests were performed on week 6, at least 24 h after the last treatment. Modified forced swim test (MFST), tail suspension test (TST) and open field test (OFT) were used followed by antioxidant markers and 5-HT levels determination.Result:Irbesartan increased swimming, climbing and decreased immobility times in MFST, decrease immobility time in TST. Irbesartan also increased no. of field crossings; rearings and also increased time spent in the centre of OFT. Thus, antidepressant like activity in UCMS mice was observed. Combination of irbesartan with fluoxetine showed potentiating effect of behavioural parameters in all animal models. Combination groups also showed antioxidant effects and elevated the 5-HT levels in UCMS mice.Conclusion:Chronic administration of Irbesartan exerted antidepressant like effect, reduced oxidative stress and elevated brain 5-HT levels.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Ayyub
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Najmi
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Akhtar
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000150:complications* / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D046353:Immobility Response, Tonic / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications* / Q000188:drug therapy; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000928:Antidepressive Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D020011:Protective Agents; D013777:Tetrazoles; D005473:Fluoxetine; D012701:Serotonin; D000077405:Irbesartan