Fachbereich Veterinärmedizin



    Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors (2004)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Kusserow, Heike
    Davies, Benjamin
    Hörtnagl, Heide
    Voigt, Ingo
    Stroh, Thomas
    Bert, Bettina
    Deng, Dong Rui
    Fink, Heidrun
    Veh, Rüdiger W
    Theuring, Franz
    Brain research. Molecular brain research; 129(1/2) — S. 104–116
    ISSN: 0169-328x
    Pubmed: 15469887
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    Tel.+49 30 838 53221 Fax.+49 30 838 53112

    Abstract / Zusammenfassung

    Serotonergic neurons play a major role in the modulation of emotion and behaviour. Especially knockout studies have revealed a role for the serotonin(1A) (5-HT(1A)) receptor in anxiety related behaviour. Mutant animals exhibit enhanced anxiety-like responses, possibly resulting from impaired autoinhibitory control of midbrain serotonergic neurons. To further elucidate the role of the 5-HT(1A) receptors in affective behaviour, a complementary approach has been used and transgenic mice overexpressing this receptor subtype have been generated. The expression of the active 5-HT(1A) receptor protein as indicated by autoradiography was transiently increased during early postnatal development (P1.5) as compared to wild-type mice. Within the next 2 weeks, the increase in receptor binding vanished and was also not apparent in adult animals indicating adaptive changes in the regulation of 5-HT(1A) receptor expression. Although no evidence for increased receptor binding in the brains of adult homozygous mice was found by autoradiography, typical phenotypic changes indicative of 5-HT(1A) receptor overactivity were apparent. Transgenic mice revealed a reduced molar ratio of 5-hydroxyindoleacetic acid to serotonin in several brain areas and elevated serotonin values in the hippocampus and striatum. Moreover, anxiety-like behaviour was decreased in male and female transgenic mice and body temperature was lowered in male transgenic mice in comparison with heterozygous and wild-type mice. These findings further underline the pivotal role of 5-HT(1A) receptors in the homeostasis of anxiety-like behaviour and the crucial importance of stimulation of the 5-HT(1A) receptor during the early postnatal development for normal anxiety-like behaviour throughout life.