Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior

Abstract

The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic–pituitary–adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS+NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS+NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.