title: The effects of long-term estradiol treatment on social behavior and gene expression in adult female rats.
abstract: This study tested the effects of long-term estradiol (E2) replacement on social behavior and gene expression in brain nuclei involved in the regulation of these social behaviors in adult female rats. We developed an ultrasonic vocalization (USV) test and a sociability test to examine communications, social interactions, and social preference, using young adult female cagemates. All rats were ovariectomized (OVX) and implanted with a Silastic capsule containing E2or vehicle, and housed in same-treatment pairs for a 3-month period. Then, rats were behaviorally tested, euthanized, and 5 nuclei in the brain's social decision-making circuit were selected for neuromolecular profiling by a multiplex qPCR method. Our novel USV test proved to be a robust tool to measure numbers and types of calls emitted by cagemates that had been reintroduced after a 1-week separation. Results also showed that E2-treated OVX rats had profoundly decreased numbers of USV calls compared to vehicle-treated OVX rats. In a test of sociability, in which a female was allowed to choose between her cagemate or a same-treatment novel rat, we found few effects of E2compared to vehicle, although interestingly, rats chose the cagemate over an unfamiliar conspecific. Gene expression results revealed that the supraoptic nucleus had the greatest number of gene changes caused by E2: Oxt, Oxtr and Avp were increased, and Drd2, Htr1a, Grin2b, and Gabbr1 were decreased, by E2. No genes were affected in the prefrontal cortex, and 1-4 genes were changed in paraventricular nucleus (Pgr), bed nucleus of the stria terminalis (Oxtr, Esr2, Dnmt3a), and medial amygdala (Oxtr, Ar, Foxp1, Tac3). Thus, E2changes communicative interactions between adult female rats, together with selected expression of genes in the brain, especially in the supraoptic nucleus.
authors.affiliation: Department of Psychology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Garcia
authors.affiliation: Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Bezner
authors.affiliation: Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Depena
authors.affiliation: Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Weiling
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Psychology, The University of Texas at Austin, Austin, TX 78712, USA; Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: andrea.gore@austin.utexas.edu.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Gore
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012919:Social Behavior; D013495:Supraoptic Nucleus / Q000187:drug effects; D013997:Time Factors
chemical_list: D004958:Estradiol
keywords: Dopamine; Epigenetics; Estradiol; Gene expression; Hypothalamus; Menopause; Oxytocin; Serotonin; Social behavior; Ultrasonic vocalization; Vasopressin