raclopride and Hypercapnia

Dopamine is related to behaviour (including arousal, motivation and motor control of locomotion), and its turnover in the brain is increased during exercise. We examined the hypothesis that dopamine D(2) receptors contribute to exercise hyperpnoea via central neural pathways using the D(2)-like receptor antagonist, raclopride. We simultaneously measured ventilation and pulmonary gas exchange for the first time in mice. Mice injected with saline and raclopride (2 mg (kg body weight)(-1); i.p.) were compared for respiratory responses to constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber. In the resting state, raclopride-treated mice had reduced respiratory frequency (f(R)) and minute ventilation (V) compared with saline-treated mice, but arterial P(CO(2)) and pulmonary gas exchange were not affected, showing that alveolar ventilation was maintained. Inhalation of hyperoxic gas maintained V in saline-treated mice, and hypercapnic ventilatory responses between the two groups were similar. Treadmill exercise produced an abrupt increase in V to a maximal level within 1 min and declined to a steady-state level in both groups. Raclopride-treated mice had reduced f(R) and V compared with saline-treated mice during steady states, but showed a similar increase in f(R) and V at exercise onset. Minute ventilation in the steady state was controlled, along with the increase in pulmonary O(2) uptake in both groups, but was lowered in raclopride-treated mice. Thus, D(2) receptors participate in resting breathing patterns to raise f(R) and exercise hyperpnoea in the steady state, probably through behavioural control and not central motor command, at exercise onset.

Topics: Animals; Blood Gas Analysis; Central Nervous System; Dopamine; Dopamine Antagonists; Hypercapnia; Hyperoxia; Male; Mice; Mice, Inbred C57BL; Oxygen Consumption; Physical Conditioning, Animal; Pulmonary Gas Exchange; Pulmonary Ventilation; Raclopride; Receptors, Dopamine D2; Respiration; Respiratory Mechanics; Respiratory Rate; Rest