Inhibition of cathecol-O-methyltransferase (COMT) in the brain does not affect the action of dopamine and levodopa: An in vitro electrophysiological evidence from rat mesencephalic dopamine neurons

Research output: Contribution to journalArticle

Abstract

In order to study whether the membrane hyperpolarization and firing inhibition caused by dopamine and levodopa on rat midbrain dopamine cells are affected by the inhibition of brain catechol-O-methyl-transferase (COMT), intracellular electrophysiological recordings were made from these neurons maintained in vitro. Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa. The lack of modification of the dopaminergic effects by tolcapone suggests that the pharmacological inhibition of intracerebral COMT does not have detectable action on dopamine neurotransmission. Therefore, the therapeutic action of tolcapone in Parkinson's disease, might be dependent on the reduction of COMT activity in the extracerebral tissue.

Original languageEnglish
Pages (from-to)1135-1140
Number of pages6
JournalJournal of Neural Transmission
Volume106
Issue number11-12
DOIs
Publication statusPublished - 1999

Fingerprint

Dopaminergic Neurons
Methyltransferases
Levodopa
Dopamine
Brain
Mesencephalon
Guaiacol
Dopamine Agents
Membranes
Transferases
Synaptic Transmission
Parkinson Disease
Pharmacology
Neurons
In Vitro Techniques
tolcapone
Therapeutics

Keywords

  • Intracellular recordings
  • Parkinson's disease
  • Substantia nigra
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Inhibition of cathecol-O-methyltransferase (COMT) in the brain does not affect the action of dopamine and levodopa: An in vitro electrophysiological evidence from rat mesencephalic dopamine neurons",
abstract = "In order to study whether the membrane hyperpolarization and firing inhibition caused by dopamine and levodopa on rat midbrain dopamine cells are affected by the inhibition of brain catechol-O-methyl-transferase (COMT), intracellular electrophysiological recordings were made from these neurons maintained in vitro. Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa. The lack of modification of the dopaminergic effects by tolcapone suggests that the pharmacological inhibition of intracerebral COMT does not have detectable action on dopamine neurotransmission. Therefore, the therapeutic action of tolcapone in Parkinson's disease, might be dependent on the reduction of COMT activity in the extracerebral tissue.",
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AU - Mercuri, N. B.

AU - Federici, M.

AU - Bernardi, G.

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