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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Bouwknecht JA,van der Gugten J,Groenink L,Olivier B,Paylor REdoi
10.1016/j.ejphar.2004.04.037keywords:
subject
Has Abstractpub_date
2004-06-21 00:00:00pages
45-53issue
1eissn
0014-2999issn
1879-0712pii
S0014299904004443journal_volume
494pub_type
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