Behavioral and physiological mouse models for anxiety: effects of flesinoxan in 129S6/SvEvTac and C57BL/6J mice.
Serotonin(1A) (5-HT(1A)) receptors are involved in anxiety. This study focuses on the role of genetic factors on the anxiety-related effects of 5-HT(1A) receptor stimulation using both a within subject design. The effects of 5-HT(1A) receptor activation were studied in high- and low-anxiety mice (129S6/SvEvTac (S6) and C57BL/6J (B6), respectively) in behavioral and physiological anxiety-related assays. These two strains were also selected because they are frequently used in gene-targeting studies. Mice were treated with the selective 5-HT(1A) receptor agonist flesinoxan (0-0.3-1.0-3.0 mg/kg s.c.) and tested in either the open-field activity test, the light-dark exploration test, or the stress-induced hyperthermia paradigm. Flesinoxan unexpectedly increased anxiety, but also decreased activity on several behavioral measures in B6 mice. Flesinoxan produced only minimal effects in the behavioral tests in the high-anxiety S6 strain. In contrast, the physiological hyperthermia response showed anxiolytic-like effects of flesinoxan in both strains. Our data indicate that the role of 5-HT(1A) receptor activation on anxiety-related responses is dependent on genetic background and selected paradigm used to assess anxiety. These findings indicate that it is critical to use a multi-level approach to develop mouse models for human diseases. In addition, the implication of such findings for studies on genetically modified mice is discussed.
Bouwknecht
J Adriaan
JA
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
van der Gugten
Jan
J
Groenink
Lucianne
L
Olivier
Berend
B
Paylor
Richard E
RE
D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D003624:Darkness; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008029:Lighting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D013045:Species Specificity
D010879:Piperazines; C056895:flesinoxan