Increased extracellular DA and normal evoked DA release in the rat striatum after a partial lesion of the substantia nigra.
After injection of 6-hydroxydopamine into the lateral part of the rat substantia nigra, tissue dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced in the corresponding lateral part of the ipsilateral caudate/putamen (CP) complex (13, 40 and 56% of controls, respectively). In this region, tyrosine hydroxylase (TH, the rate limiting enzyme of the DA synthesis) immunoautoradiography decreased by more than 80% as was the case for the binding of tritiated GBR12935 (a specific marker of the DA-carrier protein). In the medial region of the CP, only very moderate reductions of DA, DOPAC and HVA (77, 76 and 84% of controls, respectively) were observed. In this region, TH immunoautoradiography and GBR12935 binding were only reduced by about 20% reflecting weak DA denervation. However, using in vivo voltammetry, extracellular basal DA levels were found to be particularly high in the medial region of CP complex when compared to unoperated animals (up to 235%). In the medial region, TH activity was also significantly increased (161%) but the electrical stimulation of DA fibers produced the same DA overflow in control and lesioned animals. From these results, it may be concluded that elevated basal DA levels in this region cannot be attributed to the reduced DA uptake and/or to an increased ability of DA neurons to release DA in response to impulse flow.
Laboratoire de Neuropharmacologie Moléculaire, CNRS UMR 5542, Rue Guillaume Paradin, 69372 Cedex 8, Lyon, France
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Dentresangle
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Le Cavorsin
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Savasta
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Leviel
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism; D002421:Caudate Nucleus / Q000378:metabolism; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005110:Extracellular Space / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016627:Oxidopamine / Q000008:administration & dosage; D011699:Putamen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid