Sex differences in anxiety, sensorimotor gating and expression of the α4 subunit of the GABAA receptor in the amygdala after progesterone withdrawal

Maria E. Gulinello, R. Orman, S. S. Smith

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

In a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the α4 subunit of the GABAA receptor (GABAA-R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA-R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA-R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA-R α4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA-R α4 subunit in the amygdala such that α4 subunit expression was up-regulated in females during PWD whereas α4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety.

Original languageEnglish (US)
Pages (from-to)641-648
Number of pages8
JournalEuropean Journal of Neuroscience
Volume17
Issue number3
DOIs
StatePublished - Feb 2003
Externally publishedYes

Fingerprint

Sensory Gating
Startle Reflex
GABA-A Receptors
Amygdala
Sex Characteristics
Progesterone
Anxiety
Acoustics
Mood Disorders
Arousal
Brain

Keywords

  • α4 subunit
  • Acoustic startle response
  • Allopregnanolone
  • Amygdala
  • Anxiety
  • GABA receptor
  • Neurosteroid
  • Premenstrual syndrome
  • Progesterone withdrawal
  • Sex differences

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{22fdda780efa49fd9121d091fc81eeeb,
title = "Sex differences in anxiety, sensorimotor gating and expression of the α4 subunit of the GABAA receptor in the amygdala after progesterone withdrawal",
abstract = "In a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the α4 subunit of the GABAA receptor (GABAA-R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA-R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA-R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA-R α4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA-R α4 subunit in the amygdala such that α4 subunit expression was up-regulated in females during PWD whereas α4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety.",
keywords = "α4 subunit, Acoustic startle response, Allopregnanolone, Amygdala, Anxiety, GABA receptor, Neurosteroid, Premenstrual syndrome, Progesterone withdrawal, Sex differences",
author = "Gulinello, {Maria E.} and R. Orman and Smith, {S. S.}",
year = "2003",
month = "2",
doi = "10.1046/j.1460-9568.2003.02479.x",
language = "English (US)",
volume = "17",
pages = "641--648",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Sex differences in anxiety, sensorimotor gating and expression of the α4 subunit of the GABAA receptor in the amygdala after progesterone withdrawal

AU - Gulinello, Maria E.

AU - Orman, R.

AU - Smith, S. S.

PY - 2003/2

Y1 - 2003/2

N2 - In a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the α4 subunit of the GABAA receptor (GABAA-R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA-R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA-R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA-R α4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA-R α4 subunit in the amygdala such that α4 subunit expression was up-regulated in females during PWD whereas α4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety.

AB - In a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the α4 subunit of the GABAA receptor (GABAA-R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA-R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA-R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA-R α4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA-R α4 subunit in the amygdala such that α4 subunit expression was up-regulated in females during PWD whereas α4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety.

KW - α4 subunit

KW - Acoustic startle response

KW - Allopregnanolone

KW - Amygdala

KW - Anxiety

KW - GABA receptor

KW - Neurosteroid

KW - Premenstrual syndrome

KW - Progesterone withdrawal

KW - Sex differences

UR - http://www.scopus.com/inward/record.url?scp=0037325247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037325247&partnerID=8YFLogxK

U2 - 10.1046/j.1460-9568.2003.02479.x

DO - 10.1046/j.1460-9568.2003.02479.x

M3 - Article

C2 - 12581182

AN - SCOPUS:0037325247

VL - 17

SP - 641

EP - 648

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -