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Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases D1 receptor expression in carotid bodies, PVN and striatum of hamsters.
- Source :
-
Brain research [Brain Res] 2011 Jul 15; Vol. 1401, pp. 40-51. Date of Electronic Publication: 2011 May 23. - Publication Year :
- 2011
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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 0.25mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O(2) in N(2)), hypoxic (10% O(2)in 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.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Benzazepines toxicity
Carotid Body drug effects
Corpus Striatum drug effects
Cricetinae
Down-Regulation drug effects
Down-Regulation physiology
Male
Mesocricetus
Paraventricular Hypothalamic Nucleus drug effects
Receptors, Dopamine D1 biosynthesis
Respiratory Insufficiency chemically induced
Respiratory Insufficiency prevention & control
Respiratory Mechanics drug effects
Respiratory Mechanics physiology
Benzazepines pharmacology
Carotid Body metabolism
Corpus Striatum metabolism
Hypothyroidism metabolism
Paraventricular Hypothalamic Nucleus metabolism
Receptors, Dopamine D1 antagonists & inhibitors
Respiration drug effects
Respiratory Insufficiency metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1401
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 21669406
- Full Text :
- https://doi.org/10.1016/j.brainres.2011.05.034