Social reactivity and D₁ dopamine receptors: Studies in mice selectively bred for high and low levels of aggression

Robust individual differences in social behavior have been obtained by selectively breeding Institute for Cancer Research mice for high and low levels of aggression. As previously shown, when paired with a non-selected, group-housed partner mouse, NC900 mice exhibit isolation-induced aggression. Conversely, NC100 mice fail to attack, freezing upon social contact. Previous studies have established that NC100 mice have lower dopamine concentrations in nucleus accumbens and caudate nucleus, with increased dopamine receptor densities in these same regions. Thus, we wished to determine the effect of administration of a dopamine receptor agonist on social behavior. Mice of both lines were administered 0, 1, 3, or 10 mglkg (SC) of the full efficacy D₁ receptor agonist dihydrexidine, and their behavior was assessed in a social interaction test. Dihydrexidine reduced aggression in NC900 mice and nonagonistic approach in NC100 mice in a dose dependent manner. In both cases, this resulted from induction of a marked reactivity to mild social stimulation as measured by increases in behaviors such as escape, reflexive kicking, and vocalizations. Dihydrexidine had no systematic effect on the freezing behavior characteristic of the low-aggressive line. In independent experiments, mice were pretreated with either the D₁ antagonist SCH- 23390 (1.0 mg/kg) or the selective D₂ antagonist remoxipride (1.0 mg/kg), after which they received dihydrexidine (1.0 mg/ kg) and were tested as above. The effects of dihydrexidine on social reactivity in mice of both lines were significantly antagonized by SCH-23390 but not attenuated by remoxipride. Antagonist pretreatment neither reinstated attack in the NC900 line nor nonagonistic approach behavior in the NC100 line, which suggests the importance of D₁/D₂ interactions to the initiation of action. These studies suggest an important role for Di dopamine receptors in the emotional response to social stimuli.