In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during hypoxia

• Published in: Brain research 2008-01, Vol.1187, p.146-153
• Main Author: Schlenker, Evelyn H
• Format: Article
• Language: English
• Subjects: Animals; Benzazepines - pharmacology; Biological and medical sciences; Body Temperature - drug effects; Body Temperature - physiology; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cardiorespiratory control. Arterial mecano- and chemoreceptor; Carotid Body - drug effects; Carotid Body - metabolism; Carotid Body - physiopathology; Chemoreceptor Cells - drug effects; Chemoreceptor Cells - metabolism; Cricetinae; Dopamine - metabolism; Dopamine Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Hypercapnia - metabolism; Hypercapnia - physiopathology; Hypoxia - metabolism; Hypoxia - physiopathology; Male; Mesocricetus; Neurology; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - metabolism; Respiratory Insufficiency - chemically induced; Respiratory Insufficiency - physiopathology; Respiratory Physiological Phenomena - drug effects; Vertebrates: respiratory system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.10.058

Abstract During exposure of animals to hypoxia, brain and blood dopamine levels increase stimulating dopaminergic receptors which influence the integrated ventilatory response to low oxygen. The purpose of the present study is to test the hypothesis that in conscious hamsters, systemic antagonism of D1 receptors would depress their breathing in air and in response to hypoxic and hypercapnic challenges. Nine male hamsters were treated with saline or 0.25 mg/kg SCH-23390 (SCH), a D1 receptor antagonist that crosses the blood–brain barrier. Ventilation was determined using the barometric method, and oxygen consumption and CO2 production were evaluated utilizing the flow-through method. During exposure to air, SCH decreased frequency of breathing. During exposure to hypoxia (10% oxygen in nitrogen), relative to saline, SCH-treated hamsters decreased minute ventilation by decreasing tidal volume and oxygen consumption but not CO2 production. During exposure to hypercapnia (5% CO2 in 95% O2 ), frequency of breathing was decreased with SCH, but there was no significant effect on minute ventilation. Relative to saline treatment body temperature was lower in SCH-treated hamsters by 0.6 °C. These results demonstrate that in hamsters D1 receptors can modulate control of ventilation in air and during hypoxia and hypercapnic exposures. Whether D1 receptors located centrally or on carotid bodies modulate these effects is not clear from this study.