D2-Like Dopamine Receptor Mediation of Social-Emotional Reactivity in a Mouse Model of Anxiety: Strain and Experience Effects

Abstract

We examined the effects of the D2-like dopamine receptor agonist quinpirole on social-emotional reactivity in two inbred mouse strains. An important objective of this study was to determine whether these effects could be modulated by differential housing conditions (i.e., isolation versus group housing). Moreover, as motor activity is an important control for the assessment of drug effects on emotional behavior, the effects of quinpirole were tested in two inbred mouse strains (A/J and C57BL/6J) low and high in motor activity, respectively. Levels of emotional reactivity were assessed in response to mild social stimulation provided by a nonaggressive conspecific. Quinpirole increased stationary forms of reactivity (i.e., startle, kicking, defensive posture, vocalization) in both isolated and group-housed A/J mice. This effect was more pronounced and observed at lower doses in isolated than in group-housed A/J mice. Quinpirole also induced jump behavior in isolated but not group-housed A/J mice. The shift to the left in the dose-response curve of quinpirole in isolated A/J mice indicated that D2-like dopamine receptor functions can be altered by social experience. Quinpirole only marginally increased stationary and locomotor reactivity (i.e., jump) in isolated C57BL/6J mice, whereas it markedly reduced motor activity in group-housed mice of this strain. The investigation of emotional reactivity within a social context and using strains that differ in motor activity permitted the effects of drugs on emotional reactivity to be dissociated from the effects on motor activity. Given that social-emotional reactivity was elicited by what typically should have been mild and nonthreatening stimuli, this model may be highly relevant to understanding the neurobiology of anxiety. Finally, these data support an important role for dopamine in the mediation of social-emotional reactivity.

Effect of a neuraminidase inhibitor (oseltamivir) on mouse jump-down behavior via stimulation of dopamine receptors

“…Oseltamivir is a representative neuraminidase inhibitor. Slip-down behavior in mice is induced by a comparatively low-dose of the dopamine D2 receptor agonist, PPHT (17), and that the representative dopamine D2 receptor agonists morphine and quinpirole induce jump-down behavior in mice (6,10). In addition, we noticed that mouse jump-down behavior appeared by increased doses of PPHT during previous experiment.…”

Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains

“…However, to investigate hypotheses about genes underlying autism, and to evaluate potential treatments, the field needs good behavioral tasks relevant to at least a subset of the more amenable symptoms of autism. We began with two core symptoms, aberrant social interaction and resistance to change in routine, because the natural repertoire of mice includes high levels of social interaction [46,85,116,117] and some examples of perseveration [53,54,99]. Our three-chambered automated social approach task was based on existing social tasks for rodents [17,42,46,69].…”

Social Deprivation, Social–Emotional Behavior, and the Plasticity of Dopamine Function

“…Research was conducted not only in these selectively bred mice (e.g., Gariépy, Gendreau, Mailman, Tancer, & Lewis, 1995;Gariépy, Gendreau, Cairns, & Lewis, 1998) but also in other strains of mice in order to assess the generality of our findings (e.g., Gendreau, Gariépy, Petitto, & Lewis, 1997a;Gendreau, Petitto, Gariépy, & Lewis, 1998;Gendreau, Petitto, Petrova, Gariépy, & Lewis, 2000). Briefly, our findings indicated that dopamine played an important role in the mediation of specific forms of social reactivity induced by prolonged social deprivation and suggested that D1-like and D2-like dopamine receptors were differentially involved in the expression of this reactivity.…”