A course of treatments with electroconvulsive shock (ECS) has been reported to reestablish L-dopa efficacy in patients with advanced Parkinson's disease. We wished to determine if ECS could modify L-dopa and dopamine metabolism in an animal model of Parkinson's disease. Therefore, we administered repeated ECS (8 ECS at 48 hr intervals) to rats with partial destruction of the nigrostriatal dopamine pathway and used the cerebral microdialysis technique to monitor extracellular concentrations of dopamine and dopamine metabolites (DOPAC and HVA) in the corpus striatum. The control group of animals received sham-ECS treatments. Basal dopamine levels were decreased by 20% in animals receiving repeated-ECS versus sham-ECS. DOPAC levels, on the other hand, were increased by 84% in animals receiving repeated-ECS. HVA levels were equal in the two groups. Following L-dopa administration, dopamine and HVA levels increased equally in control animals and animals which had previously received repeated-ECS. DOPAC concentrations were uniformly greater in rats receiving repeated-ECS. When ECS was administered acutely, dopamine levels increased 390% and returned to baseline values in 75 minutes, DOPAC and HVA were unchanged, and 5HIAA levels decreased 30%. We conclude that 1) acute ECS administration produces a transient, marked release of striatal dopamine and 2) repeated ECS can reset the level of basal dopamine release, a finding compatible with ECS-induced dopamine receptor supersensitivity, and 3) neither single nor repeated administration of ECS has a major effect on the formation of dopamine or HVA from exogenously administered L-dopa although there was a strong tendency for increased DOPAC formation. ECS may exert its putative antiparkinsonian effect by enhancing - dopamine receptor sensitivity.
机构:
North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Wilson, Leslie R.
Lee, Christie A.
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North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Lee, Christie A.
Mason, Catherine F.
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North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Mason, Catherine F.
Khodjaniyazova, Sitora
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North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Khodjaniyazova, Sitora
Flores, Kevin B.
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North Carolina State Univ, Dept Math, Raleigh, NC 27695 USA
North Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Flores, Kevin B.
Muddiman, David C.
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North Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA
North Carolina State Univ, Mol Educ Technol & Res Innovat Ctr METRIC, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
Muddiman, David C.
Sombers, Leslie A.
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North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USANorth Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
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Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA
Univ Rochester, Dept Imaging Sci, Rochester, NY USA
Univ Rochester, Rochester Ctr Brain Imaging, Rochester, NY USAOhio State Univ, Dept Neurol, Columbus, OH 43210 USA
Tivarus, Madalina E.
Hillier, Ashleigh
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Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA
Univ Massachusetts, Dept Psychol, Lowell, MA USAOhio State Univ, Dept Neurol, Columbus, OH 43210 USA
Hillier, Ashleigh
Schmalbrock, Petra
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Ohio State Univ, Dept Radiol, Columbus, OH 43210 USAOhio State Univ, Dept Neurol, Columbus, OH 43210 USA
Schmalbrock, Petra
Beversdorf, David Q.
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Ohio State Univ, Dept Neurol, Columbus, OH 43210 USAOhio State Univ, Dept Neurol, Columbus, OH 43210 USA