title: Cotinine reduces depressive-like behavior and hippocampal vascular endothelial growth factor downregulation after forced swim stress in mice.
abstract: Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: J Alex
authors.initials: JA
authors.lastname: Grizzell
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mullins
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iarkov
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Rohani
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Charry
authors.affiliation: Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System.
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D050882:CREB-Binding Protein / Q000378:metabolism; D003367:Cotinine / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D015536:Down-Regulation / Q000187:drug effects*; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D014404:Tubulin; D042461:Vascular Endothelial Growth Factor A; D064569:alpha7 Nicotinic Acetylcholine Receptor; D050882:CREB-Binding Protein; D051528:Guanylate Kinases; D003367:Cotinine