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, an inverse 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 the early postnatal development (P1.5) as compared to wildtype 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 for overactivity of 5-HT_1A receptors 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 as compared to heterozygous and wildtype 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.