Abstract |
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.
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Authors | J Adriaan Bouwknecht, Jan van der Gugten, Lucianne Groenink, Berend Olivier, Richard E Paylor |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 494
Issue 1
Pg. 45-53
(Jun 21 2004)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 15194450
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
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Topics |
- Animals
- Anxiety
(drug therapy, genetics)
- Darkness
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Exploratory Behavior
(drug effects, physiology)
- Lighting
- Male
- Mice
- Mice, Inbred C57BL
- Piperazines
(pharmacology, therapeutic use)
- Species Specificity
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