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

Wenxia Zhou, Kathryn Cunningham, Mary L. Thomas

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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
Volume100
Issue number1-2
DOIs
StatePublished - Apr 30 2002

Fingerprint

Gene Expression Regulation
Cocaine
Estrogens
Estrogen Receptors
Hypothalamus
Mesencephalon
Messenger RNA
Brain
Amygdala
Receptor, Serotonin, 5-HT2C
Dopamine
Serotonin
Ventral Tegmental Area
Dopamine Plasma Membrane Transport Proteins
Serotonin Receptors
Nucleus Accumbens
Sprague Dawley Rats
Estradiol
Transcription Factors
Ligands

Keywords

  • Dopamine
  • Estrogen
  • mRNA
  • Serotonin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Estrogen regulation of gene expression in the brain : A possible mechanism altering the response to psychostimulants in female rats. / Zhou, Wenxia; Cunningham, Kathryn; Thomas, Mary L.

In: Molecular Brain Research, Vol. 100, No. 1-2, 30.04.2002, p. 75-83.

Research output: Contribution to journalArticle

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