The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner

Neuropsychopharmacology. 2007 Jul;32(7):1462-76. doi: 10.1038/sj.npp.1301277. Epub 2006 Dec 13.


Central dopaminergic (DA) systems appear to be particularly vulnerable to disruption by exposure to stressors in early life, but the underlying mechanisms are poorly understood. As endogenous glucocorticoids (GCs) are implicated in other aspects of neurobiological programming, this study aimed to characterize the effects of perinatal GC exposure on the cytoarchitecture of DA populations in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Dexamethasone was administered non-invasively to rat pups via the mothers' drinking water during embryonic days 16-19 or postnatal days 1-7, with a total oral intake circa 0.075 or 0.15 mg/kg/day, respectively; controls received normal drinking water. Analysis of tyrosine hydroxylase-immunoreactive cell counts and regional volumes in adult offspring identified notable sex differences in the shape and volume of the SNc and VTA, as well as the topographical organization and size of the DA populations. Perinatal GC treatments increased the DA population size and altered the shape of the SNc and VTA as well as the organization of the DA neurons by expanding and/or shifting them in a caudal direction. This response was sexually dimorphic and included a feminization or demasculinization of the three-dimensional cytoarchitecture in males, and subtle differences that were dependent on the window of exposure. These findings demonstrate that inappropriate perinatal exposure to GCs have enduring effects on the organization of midbrain DA systems that are critically important for normal brain function throughout life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Dopamine / metabolism*
  • Female
  • Glucocorticoids / adverse effects
  • Glucocorticoids / metabolism*
  • Male
  • Mesencephalon / abnormalities*
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism*
  • Nervous System Malformations / chemically induced
  • Nervous System Malformations / metabolism
  • Nervous System Malformations / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Prenatal Exposure Delayed Effects / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Sex Factors
  • Substantia Nigra / abnormalities
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / abnormalities
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism


  • Glucocorticoids
  • Tyrosine 3-Monooxygenase
  • Dopamine