Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study

Exposure to various aversive stimuli ('stressors') as well as positively-reinforcing stimuli has been shown to increase extracellular dopamine concentrations in terminal areas of the mesocorticolimbic dopamine system. The magnitude and site specificity of the dopaminergic response may depend on the nature of the aversive stimulus. In the present study, in vivo microdialysis was used to examine the effects of an ethologically relevant stressor, namely threat of social defeat, on dopamine concentrations in nucleus accumbens, striatum, and prefrontal cortex of freely-moving male Long-Evans rats. During the test session, dialysate and video recording samples were collected from previously-defeated 'intruder' rats in consecutive phases, while (1) in the home cage, (2) when placed in the empty, soiled cage of a resident rat which had previously defeated them, (3) when exposed to threat of defeat by the resident, and (4) when returned to their home cages. Control animals were not defeated; in this group of rats video recording and dialysate samples were obtained when they were placed into an empty, clean novel cage and later returned to their home cage. The results indicated that levels of dopamine were elevated to approximately 130% of baseline in nucleus accumbens and prefrontal cortex when rats were placed into either the resident or novel cage. In defeated intruders, extracellular dopamine levels in accumbens and prefrontal cortex were increased further (approximately 160% of baseline), during social threat; these biochemical changes were synchronous with high levels of orienting toward the resident but not with heightened motor activity. Extracellular dopamine levels in lateral striatum were not affected by either manipulation. These results suggest that altered accumbens and cortical extracellular dopamine concentrations during social threat are not secondary to motor activation but instead reflect increased attention to the provocative stimulus or attempts by the intruder to 'cope' with the stimulus.