Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

Evelyn H. Schlenker, Harold D Schultz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for 3 months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O 2 in N 2), hypoxic (10% O 2in N 2) and hypercapnic (5% CO 2 in O 2)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

Original languageEnglish (US)
Pages (from-to)40-51
Number of pages12
JournalBrain Research
Volume1401
DOIs
StatePublished - Jul 15 2011

Fingerprint

Carotid Body
Hypothyroidism
Cricetinae
Respiration
Hypercapnia
Ventilation
Propylthiouracil
SCH 23390
Dopamine D1 Receptors
Solitary Nucleus
Paraventricular Hypothalamic Nucleus
Carbon Monoxide
Drinking Water
Proteins

Keywords

  • Carotid body PVN
  • Hypercapnia
  • Hypothyroidism
  • Hypoxia
  • NTS
  • Propylthiouracil
  • SCH 23390

ASJC Scopus subject areas

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

Cite this

@article{2074ba0efd424c0486d0a8ac5cc06c73,
title = "Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters",
abstract = "Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04{\%} PTU in drinking water for 3 months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21{\%} O 2 in N 2), hypoxic (10{\%} O 2in N 2) and hypercapnic (5{\%} CO 2 in O 2)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.",
keywords = "Carotid body PVN, Hypercapnia, Hypothyroidism, Hypoxia, NTS, Propylthiouracil, SCH 23390",
author = "Schlenker, {Evelyn H.} and Schultz, {Harold D}",
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T1 - Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

AU - Schlenker, Evelyn H.

AU - Schultz, Harold D

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for 3 months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O 2 in N 2), hypoxic (10% O 2in N 2) and hypercapnic (5% CO 2 in O 2)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

AB - Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for 3 months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O 2 in N 2), hypoxic (10% O 2in N 2) and hypercapnic (5% CO 2 in O 2)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

KW - Carotid body PVN

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KW - Propylthiouracil

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