Mapping the neural circuit activated by alarm pheromone perception by c-Fos immunohistochemistry

We previously reported that the alarm pheromones released from stressed male rats exaggerated both behavioral and autonomic (stress-induced hyperthermia) responses in recipient rats that were introduced into a novel environment. Subsequent experiments provided evidence that these alarm pheromones could be divided into two functionally different categories based on the site specificity and testosterone dependency of their production. However, the neural mechanisms underlying these behavioral and physiological responses remain unknown. In the present study, we examined Fos expression in 26 brain sites of the recipient rat 60 min after the exposure to the pheromone that aggravated stress-induced hyperthermia. The alarm pheromone-exposed rats showed a concurrent increase in Fos expression, in contrast to control odor-exposed rats in the anterior division lateral and medial group of the bed nucleus of the stria terminalis, paraventricular nucleus, dorsomedial hypothalamic nucleus, anterodorsal medial, lateral and basolateral amygdaloid nucleus, ventrolateral periaqueductal gray, laterodorsal tegmental nucleus, and locus coeruleus. These results provide information about the neural mechanisms in response to a non-sexual pheromone, i.e., an alarm pheromone, and suggest that the perception of the alarm pheromone is related to stress-responsive brains structures, including the hypothalamus and brainstem, as well as to the amygdaloid nuclei.