MONOAMINE-OXIDASE INHIBITION CAUSES A LONG-TERM PROLONGATION OF THE DOPAMINE-INDUCED RESPONSES IN RAT MIDBRAIN DOPAMINERGIC CELLS

The way monoamine oxidase (MAO) modulates the depression of the firing rate and the hyperpolarization of the membrane caused by dopamine (DA ) on rat midbrain dopaminergic cells was investigated by means of intr acellular recordings in vitro. The cellular responses to DA, attributa ble to the activation of somatodendritic D2/3 autoreceptors, were prol onged and did not completely wash out after pharmacological blockade o f both types (A and B) of MAO. On the contrary, depression of the firi ng rate and membrane hyperpolarization induced by quinpirole (a direct D2 receptor agonist) were not affected by MAO inhibition. Furthermore , although the inhibition of DA reuptake by cocaine and nomifensine ca used a short-term prolongation of DA responses, the combined inhibitio n of MAO A and B enzymes caused a long-term prolongation of DA effects . Moreover, the effects of DA were not largely prolonged during the si multaneous inhibition of MAO and the DA reuptake system. Interestingly , the actions of amphetamine were not clearly augmented by MAO inhibit ion. From the present data it is concluded that the termination of DA action in the brain is controlled mainly by MAO enzymes. This long-ter m prolongation of the dopaminergic responses suggests a substitutive t herapeutic approach that uses MAO inhibitors and DA precursors in DA-d eficient disorders in which continuous stimulation of the dopaminergic receptors is preferable.