Serotonin receptors and animal models of aggressive behavior

Various models of rodent agonistic behavior are described, which differentiate between offensive and defensive/flight models. Particular attention is given to one male and one female paradigm for offensive aggression, i.e. resident/intruder or territorial aggression (RI) and maternal aggression (MA). After an overview of the serotonin (5-HT) system in the CNS, a description is given of the ligands available. Subsequently, the effects of various drugs affecting serotonergic transmission in the RI- and MA-paradigms are described. The 5-HT1A receptor agonists busipirone, ipsapirone, and 8-OH-DPAT decreased aggression in RI and MA, but simultaneously led to a marked decrease in social interest and activity, indicative of a nonspecific antiaggressive profile. Nonselective 5-HT1 receptor agonists, such as RU24969, eltoprazine, and TFMPP reduced aggression quite specifically, did not decrease social interest or exploration, and sometimes even increased these behaviors. In RI and MA, the behavioral effects of these drugs were roughly similar. In contrast, MA was more sensitive to treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression nonspecifically at the highest dose only. DOI, a 5-HT2A/2C# receptor agonist, decreased aggressive behavior and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by "wet dog shaking" characteristic of 5-HT2 receptor stimulation. The nonspecific 5-HT receptor agonist (and 5-HT2 receptor antagonist) quipazine also induced "wet dog shaking" at doses which suppressed aggression, social interest, and exploration but increased inactive behaviors (sitting and lying). The discussion delineates a specific role for 5-HT1B receptor-subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs, and this fact underlines the consistent role of 5-HT in different forms of aggression.