SOCIAL REACTIVITY AND D(1) 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-ind uced 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 nucleu s, with increased dopamine receptor densities in these same regions. T hus, we wished to determine the effect of administration of a dopamine receptor agonist on social behavior. Mice of both lines were administ ered 0, 1, 3, or 10 mg/kg (SC) of the full efficacy D-1 receptor agoni st dihydrexidine, and their behavior was assessed in a social interact ion test. Dihydrexidine reduced aggression in NC900 mice and nonagonis tic approach in NC100 mice in a dose dependent manner. In bath cases, this resulted from induction of a marked reactivity to mild social sti mulation as measured by increases in behaviors such as escape, reflexi ve kicking, and vocalizations. Dihydrexidine had no systematic effect on the freezing behavior characteristic of the low-aggressive fine. In independent experiments, mice were pretreated with either the D-1 ant agonist SCH-23390 (.1 mg/kg) or the selective D-2 antagonist remoxipri de (1.0 mg/kg), after which they received dihydrexidine (10 mg/kg) and were tested as above. The effects of dihydrexidine on social reactivi ty in mice of both lines were significantly antagonized by SCH-23390 b ut not attenuated by remoxipride. Antagonist pretreatment neither rein stated attack in the NC900 line nor nonagonistic approach behavior in the NC100 line, which suggests the importance of D-1/D-2 interactions to the initiation of action. These studies suggest an important role f or D-1 dopamine receptors in the emotional response to social stimuli.