Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala

The amygdala plays a pivotal role in the generation of appropriate response s to emotional stimuli. In the case of emotional stressors, these responses include activation of the hypothalamic-pituitary-adrenal (HPA) axis. This effect is generally held to depend upon the central nucleus of the amygdala , but recent evidence suggests a role for the medial nucleus. In the presen t study, c-fos expression, amygdala lesion and retrograde tracing experimen ts were performed on adult rats in order to re-evaluate the role of the cen tral as opposed to the medial amygdala in generating neuroendocrine respons es to an emotional stressor. Brief restraint (15 min) was used as a represe ntative emotional stressor and was found to elicit c-fos expression much mo re strongly in the medial than central nucleus of the amygdala; relatively few Fos-positive cells were seen in other amygdala nuclei. Subsequent exper iments showed that ibotenic acid lesions of the medial amygdala, but not th e central amygdala, greatly reduced restraint-induced activation of cells o f the medial paraventricular nucleus, the site of the tuberoinfundibular co rticotropin-releasing factor cells that constitute the apex of the HPA axis . Medial amygdala lesions also reduced the activation of supraoptic and par aventricular nucleus oxytocinergic neurosecretory cells that commonly accom panies stress-induced HPA axis activation in rodents. To assess whether the role of the medial amygdala in the control of neuroendocrine cell response s to emotional stress might involve a direct projection to such cells, retr ograde tracing of amygdala projections to the paraventricular nucleus was p erformed in combination with Fos immunolabelling. This showed that although some medial amygdala cells activated by exposure to an emotional stressor project directly to the paraventricular nucleus, the number is very small. These findings provide the first direct evidence that it is the medial rath er than the central amygdala that is critical to hypothalamic neuroendocrin e cell responses during an emotional response, and also provide the first e vidence that the amygdala governs oxytocin as well as HPA axis responses to an emotional stressor.