Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bascom DA, Clement ID, Dorrington KL, Robbins PA (1991) Effects of dopamine and domperidone on ventilation during isocapnic hypoxia in humans. Respir Physiol 85(3):319–328
Betarbet R, Sherer TB, Greenamyre JT (2002) Animal models of Parkinson’s disease. Bioessays 24(4):308–318
Bouquet CA, Gardette B, Gortan C, Abraini JH (1999) Psychomotor skills learning under chronic hypoxia. Neuroreport 10(14):3093–3099
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
Chiocchio SR, Biscardi AM, Tramezzani JH (1966) Catecholamines in the carotid body of the cat. Nature 212(5064):834–835
Dearnaley DP, Fillenz M, Woods RI (1968) The identification of dopamine in the rabbit’s carotid body. Proc R Soc Lond B Biol Sci 170(1019):195–203
Delpierre S, Fornaris M, Guillot C, Grimaud C (1987) Increased ventilatory chemosensitivity induced by domperidone, a dopamine antagonist, in healthy humans. Bull Eur Physiopathol Respir 23(1):31–35
Dumas S, Pequignot JM, Ghilini G, Mallet J, Denavit-Saubie M (1996) Plasticity of tyrosine hydroxylase gene expression in the rat nucleus tractus solitarius after ventilatory acclimatization to hypoxia. Mol Brain Res 40(2):188–194
Fernandes VS, Santos JR, Leão AH, Medeiros AM, Melo TG, Izídio GS, Cabral A, Ribeiro RA, Abílio VC, Ribeiro AM, Silva RH (2012) Repeated treatment with a low dose of reserpine as a progressive model of Parkinson’s disease. Behav Brain Res 231(1):154–163
Goiny M, Lagercrantz H, Srinivasan M, Ungerstedt U, Yamamoto Y (1991) Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. J Appl Physiol 70(6):2395–2400
Gratwicke J, Jahanshahi M, Foltynie T (2015) Parkinson’s disease dementia: a neural networks perspective. Brain 138(Pt 6):1454–1476
Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 334(6180):345–348
Hsiao C, Lahiri S, Mokashi A (1989) Peripheral and central dopamine receptors in respiratory control. Respir Physiol 76(3):327–336
Huey KA, Powell FL (2000) Time-dependent changes in dopamine D2-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia. Brain Res Mol Brain Res 75(2):264–270
Huey KA, Brown IP, Jordan MC, Powell FL (2000) Changes in dopamine D2-receptor modulation of the hypoxic ventilatory response with chronic hypoxia. Respir Physiol 123(3):177–187
Kline DD, Takacs KN, Ficker E, Kunze DL (2002) Dopamine modulates synaptic transmission in the nucleus of the solitary tract. J Neurophysiol 88(5):2736–2744
Lawrence AJ, Krstew E, Jarrott B (1995) Functional dopamine D2 receptors on rat vagal afferent neurones. Br J Pharmacol 114(7):1329–1334
Onodera H, Okabe S, Kikuchi Y, Tsuda T, Itoyama Y (2000) Impaired chemosensitivity and perception of dyspnoea in Parkinson’s disease. Lancet 356(9231):739–7340
Osanai S, Akiba Y, Matsumoto H, Nakano H, Kikuchi K (1997) Effect of dopamine receptor on hypoxic ventilatory response. Nihon Kyobu Shikkan Gakkai Zasshi 35(12):1318–1323 (Article in Japanese)
Pascual O, Roux JC, Soulage C, Morin-Surun MP, Denavit-Saubie M, Pequignot JM (2004) Carotid chemodenervation approach to study oxygen sensing in brain stem catecholaminergic cells. Methods Enzymol 381:422–448
Seccombe LM, Giddings HL, Rogers PG, Corbett AJ, Hayes MW, Peters MJ, Veitch EM (2011) Abnormal ventilatory control in Parkinson’s disease-further evidence for nonmotor dysfunction. Respir Physiol Neurobiol 179(2–3):300–304
Seccombe LM, Rogers PG, Hayes MW, Farah CS, Veitch EM, Peters MJ (2013) Reduced hypoxic sympathetic response in mild Parkinson’s disease: further evidence of early autonomic dysfunction. Parkinsonism Relat Disord 19(11):1066–1068
Serebrovskaya T, Karaban I, Mankovskaya I, Bernardi L, Passino C, Appenzeller O (1998) Hypoxic ventilatory responses and gas exchange in patients with Parkinson’s disease. Respiration 65(1):28–33
Smatresk NJ, Pokorski M, Lahiri S (1983) Opposing effects of dopamine receptor blockade on ventilation and carotid chemoreceptor activity. J Appl Physiol Respir Environ Exerc Physiol 54(6):1567–1573
Stanford SC (2007) The Open Field Test: reinventing the wheel. J Psychopharmacol 21(2):134–135
Steele RH, Hintergerge H (1972) Catecholamines and 5-hydroxytryptamine in the carotid body in vascular, respiratory, and other diseases. J Lab Clin Med 80(1):63–70
Stuss DT, Peterkin I, Guzman DA, Guzman C, Troyer AK (1997) Chronic obstructive pulmonary disease: effects of hypoxia on neurological and neuropsychological measures. J Clin Exp Neuropsychol 19(4):515–524
Walsh TS, Foo IT, Drummond GB, Warren PM (1998) Influence of dose of domperidone on the acute ventilatory response to hypoxia in humans. Br J Anaesth 81(3):322–326
Ward DS, Bellville JW (1982) Reduction of hypoxic ventilatory drive by dopamine. Anesth Analg 61(4):333–337
Welsh MJ, Heistad DD, Abboud FM (1978) Depression of ventilation by dopamine in man. Evidence for an effect on the chemoreceptor reflex. J Clin Invest 61(3):708–713
Conflicts of Interest
The authors declare no conflicts of interest with relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Bialkowska, M., Boguszewski, P., Pokorski, M. (2015). Breathing in Parkinsonism in the Rat. In: Pokorski, M. (eds) Pathophysiology of Respiration. Advances in Experimental Medicine and Biology(), vol 884. Springer, Cham. https://doi.org/10.1007/5584_2015_177
Download citation
DOI: https://doi.org/10.1007/5584_2015_177
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-24482-2
Online ISBN: 978-3-319-24484-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)