title: Effects of repeated testing in two inbred strains on flesinoxan dose-response curves in three mouse models for anxiety.
abstract: Over the last decade, many genetically modified mice have been developed as models for psychiatric diseases such as anxiety. Limited availability of such mutant mice highlights the importance of studying the possibility of repeatedly testing the same individuals. We tested mice four times with 1-week intervals with the same dose of the 5-HT(1A) receptor agonist flesinoxan (0-0.3-1.0-3.0 mg/kg s.c.) in three anxiety-related paradigms: light-dark exploration, open-field activity and stress-induced hyperthermia. The two inbred strains studied were the highly anxious 129S6/SvEvTac (S6) and low-anxiety C57BL/6J (B6) mice. The results indicate that the effects of repeated testing were relatively mild. B6 mice showed some mild habituation in the open-field test when treated with vehicle, whereas S6 mice developed reduced initial activity in the light-dark box after drug treatment. In contrast, responses to flesinoxan treatment were strong and highly consistent for most parameters. In the open-field and light-dark tests, B6 mice showed reduced activity and anxiogenic-like behavioral responses, whereas S6 mice were minimally affected. Anxiolytic-like responses were found in both strains in the stress-induced hyperthermia paradigm. We conclude that B6 and S6 mice can be tested repeatedly with agents such as 5-HT(1A) receptor agonists with 1-week intervals in the three paradigms tested.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm. S921, Houston, TX 77030, USA.
authors.forename: J Adriaan
authors.initials: JA
authors.lastname: Bouwknecht
authors.forename: Jan
authors.initials: J
authors.lastname: van der Gugten
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Richard E
authors.initials: RE
authors.lastname: Paylor
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005334:Fever / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D013045:Species Specificity
chemical_list: D010879:Piperazines; C056895:flesinoxan