title: Ondansetron, a 5HT3 receptor antagonist reverses depression and anxiety-like behavior in streptozotocin-induced diabetic mice: possible implication of serotonergic system.
abstract: Increased prevalence and high comorbidity of depression-like mood disorders and diabetes have prompted investigation of new targets and potential contributing agents. There is considerable evidence supporting the inconsistent clinical efficacy and persistent undesirable effects of existing antidepressant therapy for depression associated with diabetes. Therefore, the present study was aimed at investigating the effect of ondansetron, a selective 5HT3 receptor antagonist in attenuating depression and anxiety-like behavior comorbid with diabetes. Experimentally, Swiss albino mice were rendered diabetic by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg). After 8 weeks, diabetic mice received a single dose of vehicle/ondansetron (0.5 and 1 mg/kg, p.o.)/fluoxetine (the positive control, 10 mg/kg p.o.) for 28 days. Thereafter, behavioral studies were conducted to test depression-like behavior using forced swim test (FST) and anxiety-like deficits using hole-board and light-dark tests, followed by biochemical estimation of serotonin content in discrete brain regions. The results demonstrated that, STZ-induced diabetic mice exhibited increased duration of immobility and decreased swimming behavior in FST, reduced exploratory behavior during hole-board test and increased aversion to brightly illuminated light area in light-dark test as compared to non-diabetic mice, while ondansetron (similar to fluoxetine) treatment significantly reversed the same. Biochemical assay revealed that ondansetron administration attenuated diabetes-induced neurochemical impairment of serotonin function, indicated by elevated serotonin levels in discrete brain regions of diabetic mice. Collectively, the data indicate that ondansetron may reverse depression and anxiety-like behavioral deficits associated with diabetes in mice and modulation of serotonergic activity may be a key mechanism of the compound.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: deepaligupta2010@gmail.com.
authors.forename: Deepali
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: rmaheshbits@gmail.com.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Radhakrishnan
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India. Electronic address: yashkurhe@gmail.com.
authors.forename: Yeshwant
authors.initials: Y
authors.lastname: Kurhe
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000932:Antiemetics / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000523:psychology*; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017294:Ondansetron / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D013311:Streptozocin / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D000932:Antiemetics; D058831:Serotonin 5-HT3 Receptor Antagonists; D005473:Fluoxetine; D012701:Serotonin; D017294:Ondansetron; D013311:Streptozocin
keywords: 5HT(3) receptor antagonist; 5HT(3) receptor antagonist (PubChem CID: 4595); Anxiety; Depression; Forced swim test; Hole-board test; Streptozotocin-induced diabetes