Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats

Miklós Sárvári, Levente Deli, Pal Kocsis, L. Márk, Gábor Maász, E. Hrabovszky, I. Kalló, Dávid Gajári, Csaba Vastagh, Bálazs Siimegi, Károly Tihanyi, Z. Liposits

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERa agonist 16a-lactone-estradiol (LE2) or ERp agonist diarylpropionitrile (DPN), received a single dose of D-amphetamine-sulphate (10 mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphe- nylacetic acid content of the PFC in estradiol-replaced animals compared to ovariecto- mized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopaminecontent of the PFC. Inabroadersense ,the findings supportthe concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Volume1583
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Prefrontal Cortex
Estradiol
Estrogens
Ventral Tegmental Area
Amphetamine
Reward
Dopamine
Magnetic Resonance Imaging
3,4-Dihydroxyphenylacetic Acid
Polymerase Chain Reaction
Dopamine Plasma Membrane Transport Proteins
Dopamine Receptors
Lactones
Synaptic Transmission
Rodentia
Up-Regulation
Steroids
High Pressure Liquid Chromatography
Gene Expression
Brain

Keywords

  • Dopamine
  • Estradiol
  • Estrogen receptor alpha
  • Estrogen receptor beta
  • Mesocortical pathway
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats. / Sárvári, Miklós; Deli, Levente; Kocsis, Pal; Márk, L.; Maász, Gábor; Hrabovszky, E.; Kalló, I.; Gajári, Dávid; Vastagh, Csaba; Siimegi, Bálazs; Tihanyi, Károly; Liposits, Z.

In: Brain Research, Vol. 1583, No. 1, 2014, p. 1-11.

Research output: Contribution to journalArticle

Sárvári, Miklós ; Deli, Levente ; Kocsis, Pal ; Márk, L. ; Maász, Gábor ; Hrabovszky, E. ; Kalló, I. ; Gajári, Dávid ; Vastagh, Csaba ; Siimegi, Bálazs ; Tihanyi, Károly ; Liposits, Z. / Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats. In: Brain Research. 2014 ; Vol. 1583, No. 1. pp. 1-11.
@article{d0b472580e134e44808554a5f0f2838f,
title = "Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats",
abstract = "The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERa agonist 16a-lactone-estradiol (LE2) or ERp agonist diarylpropionitrile (DPN), received a single dose of D-amphetamine-sulphate (10 mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphe- nylacetic acid content of the PFC in estradiol-replaced animals compared to ovariecto- mized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopaminecontent of the PFC. Inabroadersense ,the findings supportthe concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain.",
keywords = "Dopamine, Estradiol, Estrogen receptor alpha, Estrogen receptor beta, Mesocortical pathway, Rat",
author = "Mikl{\'o}s S{\'a}rv{\'a}ri and Levente Deli and Pal Kocsis and L. M{\'a}rk and G{\'a}bor Ma{\'a}sz and E. Hrabovszky and I. Kall{\'o} and D{\'a}vid Gaj{\'a}ri and Csaba Vastagh and B{\'a}lazs Siimegi and K{\'a}roly Tihanyi and Z. Liposits",
year = "2014",
doi = "10.10167j.brainres.2014.06.020",
language = "English",
volume = "1583",
pages = "1--11",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats

AU - Sárvári, Miklós

AU - Deli, Levente

AU - Kocsis, Pal

AU - Márk, L.

AU - Maász, Gábor

AU - Hrabovszky, E.

AU - Kalló, I.

AU - Gajári, Dávid

AU - Vastagh, Csaba

AU - Siimegi, Bálazs

AU - Tihanyi, Károly

AU - Liposits, Z.

PY - 2014

Y1 - 2014

N2 - The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERa agonist 16a-lactone-estradiol (LE2) or ERp agonist diarylpropionitrile (DPN), received a single dose of D-amphetamine-sulphate (10 mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphe- nylacetic acid content of the PFC in estradiol-replaced animals compared to ovariecto- mized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopaminecontent of the PFC. Inabroadersense ,the findings supportthe concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain.

AB - The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERa agonist 16a-lactone-estradiol (LE2) or ERp agonist diarylpropionitrile (DPN), received a single dose of D-amphetamine-sulphate (10 mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphe- nylacetic acid content of the PFC in estradiol-replaced animals compared to ovariecto- mized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopaminecontent of the PFC. Inabroadersense ,the findings supportthe concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain.

KW - Dopamine

KW - Estradiol

KW - Estrogen receptor alpha

KW - Estrogen receptor beta

KW - Mesocortical pathway

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=84921276576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921276576&partnerID=8YFLogxK

U2 - 10.10167j.brainres.2014.06.020

DO - 10.10167j.brainres.2014.06.020

M3 - Article

C2 - 24976584

AN - SCOPUS:84921276576

VL - 1583

SP - 1

EP - 11

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -