Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors.
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.
CCR/Institut für Pharmakologie und Toxikologie, Charité, Hessische Strasse 3-4, D-10115 Berlin, Germany.
Heike
H
Kusserow
Benjamin
B
Davies
Heide
H
Hörtnagl
Ingo
I
Voigt
Thomas
T
Stroh
Bettina
B
Bert
Dong Rui
DR
Deng
Heidrun
H
Fink
Rüdiger W
RW
Veh
Franz
F
Theuring
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature; D001923:Brain Chemistry; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000737:chemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000737:chemistry
D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid