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 impul se control. To model these disorders roe have generated mice with altered s erotonergic systems. Specifically, we have created mice that lack or expres s reduced levels of two serotonin receptors: 5-HT1A and 5-HT1B receptors. T hese 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 s ome of the postsynaptic effects of serotonin. Agonists of these receptors a re currently used in the treatment of migraine and anxiety disorders. Mice lacking these receptors develop, feed, and breed normally and do not displa y any obvious abnormalities. However, when analyzed in a number of behavior al paradigms, the 5-HT1A and 5-HT1B knockout mice display a number of contr asting phenotypes. While the 5-HT1B knockout mice ave move aggressive, move reactive, and less anxious than the wild-types, the 5-HT1A knockouts are l ess reactive, more anxious, and possibly less aggressive than the wild-type s. We ave currently investigating with tissue-specific knockout mice which neural circuits are responsible for these phenotypes. (C) 1999 American Col lege of Neuropsychopharmacology. Published by Elsevier Science Inc.