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

In order to study whether the membrane hyperpolarization and firing inhibit ion caused by dopamine and levodopa on rat midbrain dopamine cells are affe cted by the inhibition of brain catechol-O-methyl-transferase (COMT), intra cellular electrophysiological recordings were made from these neurons maint ained 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 det ectable action on dopamine neurotransmission. Therefore, the therapeutic ac tion of tolcapone in Parkinson's disease, might be dependent on the reducti on of COMT activity in the extracerebral tissue.