INCREASED ANXIETY OF MICE LACKING THE SEROTONIN(1A) RECEPTOR

Brain serotonin (5-HT) has been implicated in a number of physiologica l processes and pathological conditions. These effects are mediated by at least 14 different 5-HT receptors. We have inactivated the gene en coding the 5-HT1A receptor in mice and found that receptor-deficient a nimals have an increased tendency to avoid a novel and fearful environ ment and to escape a stressful situation, behaviors consistent with an increased anxiety and stress response. Based on the role of the 5-HT1 A receptor in the feedback regulation of the 5-HT system, we hypothesi ze that an increased serotonergic neurotransmission is responsible for the anxiety-like behavior of receptor-deficient animals. This view is consistent with earlier studies showing that pharmacological activati on of the 5-HT system is anxiogenic in animal models and also in human s.