title: Mechanisms linking depression co-morbid with obesity: An approach for serotonergic type 3 receptor antagonist as novel therapeutic intervention.
abstract: Despite of the enormous research, therapeutic treatment for depression has always been a serious issue. Even though depression and obesity are individual abnormal health conditions, each act as a triggering factor for the other. Obese individuals are twice prone to develop depression than that of non-obese persons. The exact mechanism how obesity increases the risk for depression still remains an area of interest for research in neuropsychopharmacology. Depression and obesity share some common pathological pathways such as hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, dysregulation of oxidant/antioxidant system balance, higher level of inflammatory cytokines, leptin resistance, altered plasma glucose, insulin resistance, reduced neuronal brain derived neurotrophic factor (BDNF) and decreased serotonergic neurotransmission in various regions of brain. The antidepressant-like effect of 5-HT3 receptor antagonists through allosteric modulation of serotonergic pathways is well evident from several research investigations belonging to our and some in other laboratories. Furthermore, serotonin regulates diet intake, leptin, corticosterone, inflammatory mechanisms, altered plasma glucose, insulin resistance and BDNF concentration in brain. The present review deals with various biological mechanisms involved in depression co-morbid with obesity and 5-HT3 receptor antagonists by modulation of serotonergic system as a therapeutic target for such co-morbid disorder.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan 333031, India. Electronic address: yashkurhe@gmail.com.
authors.forename: Yeshwant
authors.initials: Y
authors.lastname: Kurhe
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan 333031, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015897:Comorbidity; D003866:Depressive Disorder / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology; D018384:Oxidative Stress; D010913:Pituitary-Adrenal System / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: Altered plasma glucose; Corticosterone; Depression; Leptin; Obesity