In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during hypoxia

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 D 1 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 D 1 receptor antagonist that crosses the blood-brain barrier. Ventilation was determined using the barometric method and oxygen consumption and CO 2 production were evaluated utilizing the flowthrough 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 CO 2 production. During exposure to hypercapnia (5% CO 2 in 95% O 2 ) 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 degrees Celsius. These results demonstrate that in hamsters D 1 receptors can modulate control of ventilation in air and during hypoxia and hypercapnic exposures. Whether D 1 receptors located centrally or on carotid bodies modulate these effects is not clear from this study.

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

“…The latter finding was also noted in a previous study (Schlenker, 2008). However, the relative increase in ventilation in the hypothyroid hamsters appears not to be metabolically driven, since SCH 23390 had no effect on O 2 consumption or CO 2 production.…”

“…However, the relative increase in ventilation in the hypothyroid hamsters appears not to be metabolically driven, since SCH 23390 had no effect on O 2 consumption or CO 2 production. Interestingly in a previous study in hamsters (Schlenker, 2008), a significant effect on body temperature, but not on CO 2 production was noted, but frequency of breathing (but not ventilation) was also lower following SCH 23390 treatment. Whether the difference could have be due to a circannual effect ( Summer: this study, Winter: previous study), is not clear.…”

“…This dose of SCH 23390 was used in a previous study (Schlenker, 2008). A lower dose was shown not to affect ventilation in the hamster.…”

“…SCH 23390, at a dose of 0.25 mg/kg, decreased ventilation in hamsters by decreasing frequency of breathing during exposure to room air , hypoxia, and hypercapnia (Schlenker, 2008). This was the first study to evaluate the role of D1 receptors in control of breathing in a conscious animal.…”

Brain temperature responses to salient stimuli persist during dopamine receptor blockade despite a blockade of locomotor responses

“…It also has been shown that the effects of SCH23390 (at 0.25 mg/kg or higher) on body temperature are evident within a ~3-hour duration (Faunt and Crocker, 1987; Schlenker, 2008). Since our goal was to maintain DA receptor blockade within a 4–5-hour period, our initial treatment was supplemented by an additional half-dose drug administration ~ 2.5 hours after the first injection.…”