The effect of central and peripheral dopamine-agonists on ventilation in the mouse.
This study was designed to investigate the role of central dopaminergic pathways in ventilatory control in unanaesthetised, chemoreceptor intact mice. Dopamine does not cross the blood-brain barrier and was used to selectively affect peripheral arterial chemoreceptors. Levodopa, the immediate precursor of dopamine, was given alone when it is converted to dopamine mainly in the periphery, and together with carbidopa, which prevents the peripheral conversion of levodopa to dopamine, and enhances central generation of dopamine from levodopa. Dopamine (60-240 mg X kg-1), levodopa (50-300 mg X kg-1), and levodopa with carbidopa in a constant ratio of 10:1 (33/3.3-100/10 mg X kg-1) were given by intraperitoneal injection. Ventilation was measured in 10% O2 and in 7.5% CO2 by a plethysmographic method. Levodopa with carbidopa stimulated ventilation in both 10% O2 and 7.5% CO2. Ventilation in 10% O2 increased from 55.1 +/- 1.43 ml X min-1 (mean +/- SE) to 93.8 +/- 4.75 ml X min-1 with levodopa 100 mg X kg-1/carbidopa 10 mg X kg-1 (P less than 0.01). Ventilation in 7.5% CO2 increased from 101.8 +/- 3.42 ml X min-1 to 138.5 +/- 4.94 ml X min-1 with levodopa 100 mg X kg-1/carbidopa 10 mg X kg-1 (P less than 0.05). In contrast, very high doses of dopamine alone (240 mg X kg-1) and levodopa alone (300 mg X kg-1) depressed hypoxic but not hypercapnic ventilation. Carbidopa alone had no effect of ventilation. It is concluded that dopaminergic transmission within the brain mediates pathways leading to increased ventilation.
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000502:physiology*; D002230:Carbidopa / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D010525:Peripheral Nerves / Q000502:physiology; D012119:Respiration / Q000187:drug effects*
D007980:Levodopa; D006220:Haloperidol; D002230:Carbidopa; D004298:Dopamine