ETHOPHARMACOLOGICAL STUDIES DIFFERENTIATE THE EFFECTS OF VARIOUS SEROTONERGIC COMPOUNDS ON AGGRESSION IN RATS

A series of experiments was performed to investigate the effects on aggression of various drugs affecting serotonergic transmission in rats. Using ethologically derived behavioural categories, the behaviour of treated animals was described. Drug effects were observed in two aggression models: resident-intruder aggression (RI) in male rats, and maternal aggression in lactating females during the postpartum period (MA). The 5-HT1A agonists, buspirone, 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 anti-aggressive profile. Nonselective 5-HT agonists, such as RU 24969, eltoprazine (DU 28853), and TFMPP, reduced aggression quite specifically and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA, the behavioural effects of these drugs were roughly similar. By contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only nonspecifically at the highest dose. DOI, a 5-HT2 and 5-HT1C agonist, decreased aggressive behaviour 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 agonist (and 5-HT3 antagonist) quipazine also induced "wet dog shaking" at doses that suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT 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 stressing the consistent role of 5-HT in different forms of aggression.