Serotonergic control of androgen-induced dominance

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no corresponding change in the density of 5-HT1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.