Estrogen regulation of gene expression in the brain: A possible mechanism altering the response to psychostimulants in female rats

Wenxia Zhou, Kathryn A. Cunningham, Mary L. Thomas

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Acute behavioral responses to cocaine are more pronounced in female than in male rats. We have shown that 3 weeks of treatment with 17β-estradiol (E2) implants significantly enhanced the hyperactivity induced by cocaine in ovariectomized (OVX) rats. The ligand-bound estrogen receptor (ER) functions as a transcription factor to regulate the expression of E-responsive genes. Thus, we hypothesized that estrogen (E) modulates the behavioral response to cocaine via regulation of expression of components of dopamine (DA) and serotonin (5-HT) systems in mesolimbic nuclei important in the response to cocaine as well as the hypothalamus, a brain area known to be E-responsive. Adult female Sprague-Dawley rats were OVX; half of them then received E2 implant (OVX+E) (n=8/group, two groups). Twenty-seven days later, brain tissue was collected to study E2 effects on mRNA expression for DA D1-like (D1) and D2-like (D2S, D2L, D3) receptors, DA transporter (DAT), 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C receptors, and 5-HT transporter (SERT) as well as ERα and ERβ in amygdala, hypothalamus, nucleus accumbens, midbrain, and ventral tegmental area (VTA). We found that E2 implants in OVX rats increased mRNA levels for D1 receptor in hypothalamus, D2L receptor in midbrain, and D3 receptor in VTA, and decreased D3 receptor mRNA levels in midbrain relative to OVX controls. E2 also increased 5-HT2C receptor mRNA levels in midbrain and hypothalamus. In addition, E2 decreased mRNA levels for ERα in amygdala and hypothalamus and ERβ in amygdala. The present study demonstrates that E can regulate mRNA expression for specific DA and 5-HT receptors in a region-specific manner and suggests that such modifications may contribute to the behavioral response to cocaine.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalMolecular Brain Research
Issue number1-2
StatePublished - Apr 30 2002
Externally publishedYes


  • Dopamine
  • Estrogen
  • Serotonin
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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