Absence of 5-HT1B receptors is associated with impaired impulse control in male 5-HT1B knockout mice

Background: Serotonin (5-HT) plays a complex regulatory role in processes like anxiety, depression, aggression, and impulse control. Due to the large amount of serotonergic receptors, knockout mice offer an important opportunity to investigate the role of specific receptors. The 5-HT1B receptor is thought to mediate aggression and impulse control. This was studied here in mice lacking 5-HT1B receptors (5-HT1B KO). Methods: Wild type and 5-HT1B KO mice were exposed to several types of entrained and nonentrained stimuli. With telemetry, body temperature, heart rate, and locomotor activity were measured continuously during the different experiments. Results: To nonentrained stimuli like disturbance stress and confrontation with an intruder, 5-HT1B KO mice showed exaggerated physiologic and behavioral responses. These mice displayed behavioral disinhibition, measured as increased social interest and aggression to an intruder mouse. However, in response to well-entrained stimuli like daily light transitions, responses were smaller in 5-HT1B KO than in wild type mice, suggesting that hyperreactivity is stimulus specific. Conclusions: Serotonin 1B receptors are essential in impulse control by inhibiting responses to nonentrained stimuli. Therefore, the 5-HT1B KO mouse might be an important additional model for studying aspects of disinhibition in aggression and impulse control.