Breaking away from dopamine defi ciency: An essential new direction for Parkinson ' s disease

The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre, Kyneton, Australia.
Reviews in the neurosciences (Impact Factor: 3.33). 08/2012; 23(4):403-28. DOI: 10.1515/revneuro-2012-0037
Source: PubMed


For the past 40 years Parkinson's disease (PD) has been intrinsically associated with dopamine (DA) deficiency of the nigrostriatal DA system. One of the fundamental strengths of this theoretical approach is based on a presumed relationship between the degree of DA deficiency and the severity of motor impairment in the disease and its models. However, detailed examination of a substantial number of exemplary preclinical and clinical studies reveals that any such interpretation is overoptimistic and suggests that DA deficiency may be merely an epiphenomenon of a larger process underlying this disorder. Such a conclusion is based on numerous examples of miscarriage of basic principles of good scientific practice including (i) failure to thoroughly examine the adverse effects of DA replacement, (ii) drawing of statistical inference without recognising excessive spread of measure thereby lessening the importance of outliers, (iii) confounding independent and dependent variables within the scientific paradigm, (iv) overlooking fundamental principles of modern pharmacology, (v) confusing correlation with causation in linking cause and effect and (vi) disinclination to incorporate conflicting findings thereby infringing the quintessential scientific principle of tertium quid. This review demonstrates the inherent risks and dangers in the incontrovertible defence of DA deficiency theory and serves to address the ethical problems that emerge from the clinical application of scientific findings. There is increasing interest in new directions for PD research by dimming down the current emphasis on the importance of DA deficiency and its replacement. This would provide genuine hope and a new direction for the sufferers of a most debilitating disease.

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    • "Dopamine (DA) is involved in different functions of the nervous system like cognition, reward mechanisms, motor functions, learning, and memory. In the striatum, DA modulates synaptic transmission and synaptic plasticity through the activation of its DA receptors [1] [2] [3] [4]. The modulation of DA depends on receptor subtype stimulated in a particular synapse; for example, activation of D1-class dopamine receptors (D1) increases glutamatergic responses mediated by Nmethyl-D-aspartate (NMDA) and non-NMDA receptors in the corticostriatal pathway, and the stimulation of D2-class dopamine receptors (D2) attenuates them [5] [6]. "
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