Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors

Dysfunctions of the serotonergic system have been implicated in a number of psychiatric disorders including depression, anxiety and disorders of impulse control. To model these disorders roe have generated mice with altered serotonergic systems. Specifically, we have created mice that lack or express reduced levels of two serotonin receptors: 5-HT1A and 5-HT1B receptors. These receptors are localized both on serotonergic neurons where they act as autoreceptors and on non-serotonergic neurons. As a result, the 5-HT1A and 5-HT1B receptors control the tone of the serotonergic system and mediate some of the postsynaptic effects of serotonin. Agonists of these receptors are currently used in the treatment of migraine and anxiety disorders. Mice lacking these receptors develop, feed, and breed normally and do not display any obvious abnormalities. However, when analyzed in a number of behavioral paradigms, the 5-HT1A and 5-HT1B knockout mice display a number of contrasting phenotypes. While the 5-HT1B knockout mice ave move aggressive, move reactive, and less anxious than the wild-types, the 5-HT1A knockouts are less reactive, more anxious, and possibly less aggressive than the wild-types. We ave currently investigating with tissue-specific knockout mice which neural circuits are responsible for these phenotypes. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.