title: Cotinine enhances the extinction of contextual fear memory and reduces anxiety after fear conditioning.
abstract: Posttraumatic stress disorder (PTSD) is an anxiety disorder triggered by traumatic events. Symptoms include anxiety, depression and deficits in fear memory extinction (FE). PTSD patients show a higher prevalence of cigarette smoking than the general population. The present study investigated the effects of cotinine, a tobacco-derived compound, over anxiety and contextual fear memory after fear conditioning (FC) in mice, a model for inducing PTSD-like symptoms. Two-month-old C57BL/6J mice were separated into three experimental groups. These groups were used to investigate the effect of pretreatment with cotinine on contextual fear memory and posttreatment on extinction and stability or retrievability of the fear memory. Also, changes induced by cotinine on the expression of extracellular signal-regulated kinase (ERK)1/2 were assessed after extinction in the hippocampus. An increase in anxiety and corticosterone levels were found after fear conditioning. Cotinine did not affect corticosterone levels but enhanced the extinction of contextual fear, decreased anxiety and the stability and/or retrievability of contextual fear memory. Cotinine-treated mice showed higher levels of the active forms of ERK1/2 than vehicle-treated mice after FC. This evidence suggests that cotinine is a potential new pharmacological treatment to reduce symptoms in individuals with PTSD.
authors.affiliation: Bay Pines VA Healthcare System, Bay Pines, FL 33744, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Zeitlin
authors.forename: Sagar
authors.initials: S
authors.lastname: Patel
authors.forename: Rosalynn
authors.initials: R
authors.lastname: Solomon
authors.forename: John
authors.initials: J
authors.lastname: Tran
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
authors.forename: Valentina
authors.initials: V
authors.lastname: Echeverria
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D003367:Cotinine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005239:Fear / Q000187:drug effects*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000187:drug effects; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D003367:Cotinine; D003345:Corticosterone