Dopaminergic activation of estrogen receptors in neonatal brain alters progestin receptor expression and juvenile social play behavior

Endocrinology. 2005 Sep;146(9):3705-12. doi: 10.1210/en.2005-0498. Epub 2005 May 26.


Steroid receptor activation in developing brain influences a variety of cellular processes that endure into adulthood, altering both behavior and physiology. We report that estrogen receptors can be activated in a ligand-independent manner within developing brain by membrane dopamine receptors. Neonatal treatment with either estradiol or a dopamine D1 receptor agonist can increase the expression of an estrogen receptor-regulated gene (i.e. progestin receptors) and later juvenile social play. More importantly, increases in social play behavior induced by neonatal treatment with estradiol or a dopamine D1 receptor agonist can be prevented by prior treatment with an estrogen receptor antagonist. This suggests that changes in dopamine transmission in developing brain can activate estrogen receptors in a ligand-independent manner to influence gene expression and have lasting consequences on social behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Brain / growth & development*
  • Brain / metabolism
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Male
  • Play and Playthings
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Progesterone / metabolism*
  • Social Behavior
  • Tamoxifen / pharmacology


  • Dopamine Agonists
  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Receptors, Dopamine D1
  • Receptors, Progesterone
  • Tamoxifen
  • Estradiol
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Dopamine