5-HT1B receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running

Abstract

Serotonin 5-HT(1B) receptors are promising targets for the management of several mood and impulse disorders. These experiments examine a 5-HT(1B) agonist, CP-94,253, and attempt to distinguish between its effects on seeking to perform three rewarding behaviors: aggression, drinking, and wheel running. Male CFW mice perform nose-poke responses that are maintained by a fixed interval schedules of 10-min (FI10) schedule to gain access to one of three rewarding activities. The first experiment studies mice reinforced by the opportunity to confront an intruder mouse after drinking water or alcohol; the second studies mice reinforced by the presentation of alcoholic or non-alcoholic solutions (i.e., 6% ethanol, 0.05% saccharin vs 0.05% saccharin); the third studies mice reinforced by access to a running wheel. CP-94,253 (1.0-10 mg/kg i.p.) dose-dependently reduces aggression, drinking, and wheel running. Of these behaviors, alcohol-heightened aggression is the most sensitive to the 5-HT(1B) receptor agonist (ED50 = 4.8 mg/kg). Responding for the opportunity to drink or engage in alcohol-heightened aggression is suppressed by the highest dose of CP-94,253, whereas CP-94,253 does not affect responding that is reinforced by wheel running or species-typical aggression. These results confirm the inhibitory effects of 5-HT(1B) receptor stimulation on aggressive performance and drinking. They also reveal an inhibition of voluntary wheel running, contrary to the stimulation of running in a novel, open arena. 5-HT(1B) receptor agonists may be particularly useful for the treatment of aggressive behavioral disorders, but their efficacy and potency appear to be sensitive to the intensity and context of the behavior.