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Sex Differences in Serotonergic But Not -Aminobutyric Acidergic (GABA) Projections to the Rat Ventromedial Nucleus of the Hypothalamus

Department of Zoology (H.B.P.), North Carolina State University, Raleigh, North Carolina 27695; CIIT Centers for Health Research (H.B.P., A.E.F., E.K.P.), Research Triangle Park, North Carolina 27709; Department of Epidemiology (A.E.F.), University of North Carolina, Chapel Hill, North Carolina 27519; and Department of Physiology and Biophysics (E.K.P.) and Specialized Neuroscience Research Program (E.K.P.), Howard University College of Medicine, Washington, DC 20059

Address all correspondence and requests for reprints to: Dr. Heather Patisaul, Department of Zoology, North Carolina State University, Raleigh, North Carolina 27695. E-mail: heather_patisaul{at}ncsu.edu.

Hormonal conditions that elicit lordosis in female rats are ineffective in males, suggesting that this behavior is actively suppressed in males. Previous studies theorize that serotonergic and -aminobutyric acidergic (GABA) inputs to the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMNvl) may contribute to lordosis inhibition in males. Using triple-label immunofluorescent techniques, the present studies explored potential sex differences in the density of these projections within three hypothalamic sites: the VMNvl, the arcuate nucleus (ARC), and the dorsomedial nucleus of the hypothalamus. Antibodies directed against HuC/D, estrogen receptor (ER)- and either serotonin (5-HT) or the -aminobutyric acid synthetic enzyme glutamic acid decarboxylase-65 were used to compare the densities of glutamic acid decarboxylase (GAD)-65- and 5-HT-containing fibers in each brain area, the percentage of VMNvl HuC/D immunoreactive (ir) neurons that contained ER, and the percentage of HuC/D and ER double-labeled cells receiving apparent contacts from 5-HT fibers between adult, gonadectomized male and female rats. The densities of VMNvl and ARC 5-HT immunolabeled fibers were significantly higher in the males, and the percentage of VMNvl HuC/D-ir neurons containing ER was significantly higher in the females. The percentage of HuC/D-ir cells contacted by 5-HT fibers was significantly higher in the males, compared with the females, but there was no sex difference in the proportion of those cells receiving contacts that were ER-ir. Neonatal administration of estradiol but not genistein masculinized 5-HT content in the adult female VMNvl, but the percentage of HuC/D-ir cells colabeled with ER was not significantly affected by treatment. A similar, but not statistically significant, pattern was observed in the ARC. These findings suggest that the development of serotonergic inputs to the male VMNvl is orchestrated by neonatal estradiol exposure. The hormone-dependent organization of these 5-HT projection patterns may be an important developmental mechanism accounting for sex-specific behaviors in adulthood.