Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function

Michael J. Weiser, Chad D. Foradori, Robert J Handa

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Neuropsychiatric disorders such as anxiety and depression have formidable economic and societal impacts. A dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis leading to elevated endogenous glucocorticoid levels is often associated with such disorders. Chronically high glucocorticoid levels may act upon the central nucleus of the amygdala (CeA) to alter normally adaptive responses into those that are maladaptive and detrimental. In addition to glucocorticoids, other steroid hormones such as estradiol and androgens can also modify hormonal and behavioral responses to threatening stimuli. In particular, estrogen receptor beta (ERβ) agonists have been shown to be anxiolytic. Consequently, these experiments addressed the hypothesis that the selective stimulation of glucocorticoid receptor (GR) in the CeA would increase anxiety-like behaviors and HPA axis reactivity to stress, and further, that an ERβ agonist could modulate these effects. Young adult female Sprague-Dawley rats were ovariectomized and bilaterally implanted via stereotaxic surgery with a wax pellet containing the selective GR agonist RU28362 or a blank pellet, to a region just dorsal to the CeA. Four days later, animals were administered the ERβ agonist S-DPN or vehicle (with four daily sc injections). Anxiety-type behaviors were measured using the elevated plus maze (EPM). Central RU28362 implants caused significantly higher anxiety-type behaviors in the EPM and greater plasma CORT levels than controls given a blank central implant. Moreover, S-DPN treated animals, regardless of type of central implant, displayed significantly lower anxiety-type behaviors and post-EPM plasma CORT levels than vehicle treated controls or vehicle treated animals implanted with RU28362. These results indicate that selective activation of GR within the CeA is anxiogenic, and peripheral administration of an ERβ agonist can overcome this effect. These data suggest that estradiol signaling via ERβ prevents glucocorticoid-dependent effects of the CeA on behavior and neuroendocrine function.

Original languageEnglish (US)
Pages (from-to)78-88
Number of pages11
JournalBrain Research
Volume1336
DOIs
StatePublished - Jun 8 2010

Fingerprint

Estrogen Receptor beta
Glucocorticoid Receptors
Anxiety
Glucocorticoids
Estrogens
NAD
Estradiol
Waxes
Anti-Anxiety Agents
Androgens
Sprague Dawley Rats
Young Adult
Steroids
Economics
Central Amygdaloid Nucleus
Hormones
Depression
Injections

Keywords

  • Amygdala
  • Anxiety
  • Estrogen receptor
  • Glucocorticoids
  • Stereotaxic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function. / Weiser, Michael J.; Foradori, Chad D.; Handa, Robert J.

In: Brain Research, Vol. 1336, 08.06.2010, p. 78-88.

Research output: Contribution to journalArticle

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