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ABSTRACT: Re: A New compensation model of Preclinical Parkinsonism. Journal of Neurochemistry, Vol. 87, No. 5, 2003 1224-1236 © 2003 International Society for Neurochemistry ‘Passive stabilization’ of striatal extracellular dopamine across the lesion spectrum encompassing the presymptomatic phase of Parkinson's disease: a voltammetric study in the 6-OHDA-lesioned rat Brian P. Bergstrom* and Paul A. Garris * Department of Biology, Muskingum College, New Concord, Ohio, USA Cellular and Integrative Physiology Section, Department of Biological Sciences, Illinois State University, Normal, Illinois, USA Address correspondence and reprint requests to Paul A. Garris, PhD, 210 Julian Hall, Department of Biological Sciences, Illinois State University, Normal, IL 61790–4120, USA. E-mail: [log in to unmask] Symptoms of Parkinson's disease do not present until the degeneration of nigrostriatal dopaminergic neurons is nearly complete. Maintenance of dopaminergic tone governing striatal efferents is postulated to preserve motor control during the presymptomatic phase, but the neuroadaptation responsible for normalization is not completely understood. In particular, the prevailing view that surviving dopaminergic neurons compensate by up-regulating release has been difficult to demonstrate directly. Here we investigate dopaminergic neurotransmission in the hemiparkinsonian rat using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Electrical stimulation was used to elicit extracellular dopamine levels mimicking the steady-state dynamics of tonic dopaminergic signaling. In agreement with microdialysis studies, evoked steady-state dopamine levels remained constant over the entire lesion spectrum (0 to 85%) observed during the presymptomatic stage. Kinetic analysis of the voltammetric recordings demonstrated that evoked dopamine concentrations were normalized without plasticity of dopamine release and uptake, suggesting that the primary mechanisms controlling ambient levels of extracellular dopamine were not actively altered. In the present study, we formalize this neuroadaptation as ‘passive stabilization’. We further propose that passive stabilization is mediated by the simple physical principles of diffusion and steady state, is predicated on extrasynaptic transmission, and forms the basis for a new compensation model of preclinical parkinsonism. Key Words: compensation – dopamine – Parkinson's disease – release – uptake – voltammetry Abbreviations used: DA, dopamine; 6-OHDA, 6-hydroxydopamine; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine SOURCE: The Journal of Neurochemistry http://www.jneurochem.org/cgi/content/abstract/87/5/1224 * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn