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 re activity to mild social stimulation. Aggression, social avoidance and a var iety of defensive behaviors that differ in terms of motor activation (e.g. freezing, escape) can be observed depending on strain. previous studies sug gested that D-2-like dopamine (DA) receptors play an important, albeit stra in specific, role in the mediation of particular forms of defensive behavio r. D-3 receptors are subtypes of D-2-like receptors that are highly express ed in limbic areas of the brain and, therefore, they have been hypothesized to mediate emotional behavior. This study examined the effects of the puta tive D-3 receptor agonists 7-OH-DPAT and PD128907 on social-emotional behav ior in isolated C57BL/6J and A/J mice. These effects were compared with tho se of the selective D-2 receptor agonist PNU91356A. All three DA agonists i ncreased non-locomotor forms of defensive behavior (e.g. freezing, upright defensive posture). These effects were observed at low doses ill C57BL/6J a nd at higher doses in A/J mice. Only the D-3 receptor agonists were effecti ve 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 poten tiate defensive behavior and/or social fearfulness. They also suggest that D-3 and D-2 DA receptors differentially modulate the expression of social-e motional reactivity and indicate the importance of strain in examining the effects of DA ligands on emotional behavior. (C) 2000 Elsevier Science B.V. All rights reserved.