Breathing in Parkinsonism in the Rat
Parkinsonism is underlain by dopamine (DA) deficiency in the mid-brain, a neurotransmitter innately involved with respiratory regulation. However, the state of respiration in parkinsonism is an unsettled issue. In this study we seek to determine ventilation and its responses to hypoxia in a reserpine – alpha-methyl-tyrosine model of parkinsonism in the rat. We also attempted to differentiate between the role of discrete brain and carotid body DA stores in the modulation of the hypoxic ventilatory response (HVR). To this end we used domperidone, a peripheral D2 receptor antagonist, and levodopa, a central D2 receptor agonist. The HVRs to acute 12 % and 8 % hypoxia were studied in a whole body plethysmograph in the same rats before and after the induction of parkinsonic symptoms in conscious rats. We found that resting ventilation and the HVR were distinctly reduced in parkinsonism. The reduction was particularly evident in the peak hypoxic hyperpneic augmentation. Domperidone, which enhanced ventilation in the control healthy condition, failed to reverse the reduced parkinsonic HVR. In contrast, levodopa, which did not appreciably affected ventilation in the healthy condition, caused the parkinsonic HVR to return to and above the baseline healthy level. The findings demonstrate the predominance of a lack of the central DA stimulatory element and minimize the role of carotid body DA in the ventilatory impediment of parkinsonism. In conclusion, the study provides the pathophysiological savvy concerning the respiratory insufficiency of parkinsonism, a sequela which carries a risk of chronically impaired blood oxygenation, which may drive the disease worsening.
KeywordsDomperidone Dopamine Hypoxic ventilatory response Levodopa Parkinsonism Reserpine Ventilation
- Chang CH, Grace AA (2015) Amygdala neuronal activity: Differential D1 and D2 receptor effects on thalamic and cortical afferent inputs. Int J Neuropsychopharmacol 18(8). pii: pyv015. doi:10.1093/ijnp/pyv015