Submitted on July 9, 2007
Accepted on September 5, 2007
Thyroid Status affects 5-HT2A Receptor Modulation of Breathing Before, During and Following Exposure of Hamsters to Acute Intermittent Hypoxia
Abrea A. Varney1 and Evelyn Heymann Schlenker1*
1 Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, Vermillion, South Dakota, United States
* To whom correspondence should be addressed. E-mail: Evelyn.Schlenker{at}usd.edu.
The BIO 14.6 hamster (dystrophic), animal model of limb girdle muscular dystrophy, exhibits low plasma triiodothyronine levels, muscle weakness, and decreased breathing. After exposure to acute intermittent bouts of hypoxia (IH), dystrophic hamsters depress ventilation relative to baseline resulting in ventilatory long-term depression (LTD). Control hamsters may increase ventilation relative to baseline resulting in ventilatory long-term facilitation (LTF). Serotonin (5-HT) receptors, especially the 5-HT2A subtype, are involved in the development of LTF. The purpose of this study was to evaluate the role of 5-HT2A receptors in ventilatory and metabolic responses before, during, and following IH in eleven euthyroid, nine dystrophic, and eleven propylthiouracil (PTU)-induced hypothyroid male hamsters. Animals received subcutaneous injections of vehicle or 0.5 mg/kg MDL (5-HT2A receptor antagonist). Plethysmography was used to evaluate ventilatory responses of the three groups to air, five bouts of five minutes of 10% oxygen each interspersed with five minutes of air, followed by 60 minutes of exposure to air. CO2 production was measured using the flow-through method. Vehicle-treated dystrophic and PTU- treated hamsters exhibited LTD. MDL decreased body temperature in all groups. After MDL treatment, the euthyroid group exhibited LTD. MDL treatment in the dystrophic, but not in the PTU-treated hamsters, maintained tidal volume, but did not reverse LTD. CO2 production was increased in the euthyroid group with MDL treatment. Thus, 5-HT2A receptors affect body temperature, ventilation, and metabolism in hamsters. The differential responses noted in this study may be in part dependent on thyroid hormone status.
