D(3) and D(2) dopamine receptor agonists differentially modulate isolation-induced social-emotional reactivity in mice.

Following isolation housing, mice typically exhibit heightened emotional reactivity to mild social stimulation. Aggression, social avoidance and a variety of defensive behaviors that differ in terms of motor activation (e.g. freezing, escape) can be observed depending on strain. Previous studies suggested that D(2)-like dopamine (DA) receptors play an important, albeit strain specific, role in the mediation of particular forms of defensive behavior. D(3) receptors are subtypes of D(2)-like receptors that are highly expressed in limbic areas of the brain and, therefore, they have been hypothesized to mediate emotional behavior. This study examined the effects of the putative D(3) receptor agonists 7-OH-DPAT and PD128907 on social-emotional behavior in isolated C57BL/6J and A/J mice. These effects were compared with those of the selective D(2) receptor agonist PNU91356A. All three DA agonists increased non-locomotor forms of defensive behavior (e.g. freezing, upright defensive posture). These effects were observed at low doses in C57BL/6J and at higher doses in A/J mice. Only the D(3) receptor agonists were effective in increasing locomotor forms of defensive behavior (i.e. escape, jump) at higher doses. These effects were more pronounced in C57BL/6J mice than A/J mice. The increases in stationary and locomotor defensive behavior were accompanied by marked reduction in social investigation in both the strains. Aggressive behavior was also abolished in the aggressive C57BL/6J strain. These results support previous findings and suggest that DA agonists potentiate defensive behavior and/or social fearfulness. They also suggest that D(3) and D(2) DA receptors differentially modulate the expression of social-emotional reactivity and indicate the importance of strain in examining the effects of DA ligands on emotional behavior.