Thyroid status affects 5-HT2A receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia

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, 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-HT(2A) subtype, are involved in the development of LTF. The purpose of this study was to evaluate the role of 5-HT(2A) receptors in ventilatory and metabolic responses before, during, and following intermittent hypoxia 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-HT(2A) receptor antagonist). Plethysmography was used to evaluate ventilatory responses of the three groups to air, five bouts of 5 min of 10% oxygen, each interspersed with 5 min of air, followed by 60 min of exposure to air. CO(2) 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. CO(2) production was increased in the euthyroid group with MDL treatment. Thus, 5-HT(2A) 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.