5-HT1B RECEPTOR KNOCK OUT - BEHAVIORAL CONSEQUENCES

Serotonin is a neuromodulator that is involved in a number of mood dis orders such as depression, anxiety and impulsive violence. In an attem pt to dissect the contribution of individual 5-HT receptor subtypes to behavior, we have generated by homologous recombination, mutant mice lacking the 5-HT1B receptor. These mice did not exhibit any obvious de velopmental or behavioral defect. However, the hyperlocomotor effect o f the 5-HT1A/1B agonist, RU 24969 was completely absent in mutant mice , indicating that this effect is mediated by 5-HT1B receptors. Moreove r, when confronted with an intruder, isolated mutant mice attacked the intruder faster and more intensely than wild-type mice, suggesting an involvement of 5-HT1B receptors in the modulation of aggressive behav ior. These data might be related to the fact that a class of 5-HT1 ago nists, termed serenics, have anti-aggressive properties, and with the findings that certain impulsive aggressive behaviors are associated wi th deficits in central serotonin.