Neonatal inhibition of brain estrogen synthesis alters adult neural Fos responses to mating and pheromonal stimulation in the male rat.

Neonatal inhibition of brain estrogen formation in male rats by administration of the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), permanently changes aspects of their mating behavior and partner preference in adulthood. The medial preoptic area receives chemosensory inputs via a sexually dimorphic vomeronasal projection circuit, which responds to reproductively relevant pheromonal cues. The medial preoptic area also receives genital somatosensory inputs via the midbrain central tegmental field and the medial amygdala. We used Fos immunoreactivity as a marker of neuronal activation to determine whether there is a correspondence between the behavioral profiles of neonatally ATD-treated male rats and their neuronal responses in the medial preoptic area and other brain regions to somatosensory and chemosensory stimuli. Achieving eight intromissions with an estrous female led to a greater neuronal Fos immunoreactivity in the medial preoptic area of neonatally ATD-treated male rats compared with neonatally cholesterol-treated male rats. Exposure for 1.5 h to chemosensory cues derived from soiled bedding of estrous females induced Fos immunoreactivity throughout the vomeronasal pathway (i.e. medial amygdala, bed nucleus of the stria terminalis and medial preoptic area) in both ATD and cholesterol males (Experiment 2a). By contrast, exposure for 1.5 h to chemosensory cues derived from soiled bedding of sexually active males revealed clear differences between ATD and cholesterol males in neuronal Fos immunoreactive (Experiment 2b). At peripheral portions of the vomeronasal pathway (i.e. the accessory olfactory bulb and the medial amygdala), there were no differences in the number of Fos immunoreactivity neurons between ATD and cholesterol males. However, neurons in the more central portions of the vomeronasal pathway (i.e. the bed nucleus of the stria terminalis and the medial preoptic area) showed increased Fos immunoreactivity after exposure to odors from sexually active males in ATD males as opposed to cholesterol males. Females, like ATD males, showed neuronal Fos immunoreactivity at each level of the vomeronasal pathway after being exposed to odors from sexually active males. These results suggest that the responsiveness of neurons in the central portion of the vomeronasal projection circuit to odors from sexually active males, but not estrous females, is sexually differentiated in male rats due to the neonatal action of estrogens.