Effects of serotonergic agents on isolation-induced aggression.

A series of serotonergic agents were assessed for their ability to antagonize isolation-induced aggression and their activity to disrupt performance in the rotorod motor coordination test. All compounds with 5-HT1A activity [buspirone, gepirone, ipsapirone, tandospirone (SM-3997), 8-OH-DPAT, Wy-48,723, BMY-7378, Wy-47,846] reduced aggression at doses below those which produced debilitation in the rotorod motor coordination test. In addition, the 5-HT3 antagonist zacopride failed to attenuate aggression or produce debilitation at any of the doses tested; however, the 5-HT2 antagonist ritanserin inhibited aggressive behavior at a high dose which was not debilitating. Benzodiazepines (chlordiazepoxide, diazepam and lorazepam), and antidepressant (desipramine) and an antipsychotic (haloperidol) reduced aggressive behavior only at debilitating doses. Activity at the 5-HT1A receptor, and possibly nonsedative anxiolytic activity, appears to be related to antagonism of isolation-induced aggression.