Estrogen receptor-beta immunoreactivity in the midbrain of adult rats: regional, subregional, and cellular localization in the A10, A9, and A8 dopamine cell groups

J Comp Neurol. 2002 May 6;446(3):288-300. doi: 10.1002/cne.10207.


Estrogen modulates dopamine synthesis, release, and metabolism in corticolimbic and striatal targets of midbrain dopamine neurons. The relevant sites of receptor-mediated action, however, had been elusive, because all available evidence suggested a paucity of intracellular estrogen receptors in the A8, A9, and A10 dopamine regions and their afferent targets. More recent evidence of a relative abundance of the beta isoform of the estrogen receptor (ER) in the substantia nigra and ventral tegmental area (VTA), however, suggests that this newly described receptor may be important in estrogen's stimulation of midbrain DA systems. It is unknown, however, precisely how ERbeta is distributed with respect to the functionally and neurochemically diverse cell populations of the ventral midbrain. To address these issues, this study used single- and double-label immunocytochemistry to detail the regional, subregional, and cellular distributions of ERbeta immunoreactivity in and around midbrain dopamine-containing cell groups in hormonally intact adult male and female rats. These analyses revealed that ERbeta-immunoreactive nuclei were found only in neurons, more specifically, within subsets of both dopaminergic and nondopaminergic neurons in the dorsal VTA, the parabrachial pigmented nucleus, the substantia nigra pars lateralis, the retrorubral fields, and to a lesser extent the linear midline nuclei. These regional and cellular receptor distributions thus place the ERbeta isoform in anatomical register with midbrain dopamine systems known to participate in a spectrum of motor, cognitive, and affective functions.

Publication types

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

MeSH terms

  • Animals
  • Dopamine / physiology*
  • Estrogen Receptor beta
  • Estrous Cycle / physiology
  • Female
  • Immunohistochemistry
  • Male
  • Mesencephalon / cytology
  • Mesencephalon / metabolism*
  • Mesencephalon / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / metabolism*
  • Sex Characteristics
  • Tegmentum Mesencephali / cytology
  • Tegmentum Mesencephali / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Estrogen Receptor beta
  • Receptors, Estrogen
  • Tyrosine 3-Monooxygenase
  • Dopamine