title: Citalopram protects against cold-restraint stress-induced activation of brain-derived neurotrophic factor and expression of nuclear factor kappa-light-chain-enhancer of activated B cells in rats.
abstract: The present study evaluates the protective effect of citalopram against cold-restraint stress (CRS) paradigm. Rats were pretreated with citalopram (0.1, 1.0, and 10.0 mg/kg) acutely and repeatedly for 21 days before exposure to the CRS procedure. None of the doses of citalopram attenuated CRS-induced gastric ulcers in the acute study. In contrast, repeated pretreatment of citalopram at a dose level of 0.1 mg/kg attenuated the CRS-induced gastric ulcers. Citalopram (0.1 mg/kg) diminished CRS-induced increase in plasma corticosterone, but not plasma norepinephrine level in the chronic study indicating its effect on hypothalamic-pituitary-adrenal axis function. Repeated citalopram (0.1 mg/kg) pretreatment attenuated CRS-induced changes in serotonin turnover in the hippocampus and amygdala. Moreover, repeated pretreatment with citalopram (0.1 mg/kg) mitigated the CRS-induced increase in the expression of brain-derived neurotrophic factor (BDNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) in the hippocampus and amygdala. These results suggest that there is a region- and a dose-specific effect of citalopram on CRS-induced BDNF-NFκB activation. Therefore, citalopram showed antistress activity in the CRS model through changes in the stress-responsive pathways such as hypothalamic-pituitary-adrenal-axis and brain serotonergic system apart from decreasing the expression of BDNF and NFκB.
authors.affiliation: Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India.
authors.forename: Debapriya
authors.initials: D
authors.lastname: Garabadu
authors.forename: B C M Harshavardhan
authors.initials: BC
authors.lastname: Reddy
authors.forename: Sairam
authors.initials: S
authors.lastname: Krishnamurthy
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D058639:Cold-Shock Response; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D012701:Serotonin / Q000097:blood; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram; D003345:Corticosterone; D016328:NF-kappa B; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors