TY - JOUR
T1 - Monoamine oxidase inhibition causes a long-term prolongation of the dopamine-induced responses in rat midbrain dopaminergic cells
AU - Mercuri, Nicola B.
AU - Scarponi, Mariangela
AU - Bonci, Antonello
AU - Siniscalchi, Antonio
AU - Bernardi, Giorgio
PY - 1997
Y1 - 1997
N2 - 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 intracellular recordings in vitro. The cellular responses to DA, attributable to the activation of somatodendritic D2/3 autoreceptors, were prolonged and did not completely wash out after pharmacological blockade of both types (A and B) of MAO. On the contrary, depression of the firing 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 caused a short-term prolongation of DA responses, the combined inhibition 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 simultaneous inhibition of MAO and the DA reuptake system. Interestingly, the actions of amphetamine were not clearly augmented by MAO inhibition. From the present data it is concluded that the termination of DA action in the brain is controlled mainly by MAO enzymes. This long- term prolongation of the dopaminergic responses suggests a substitutive therapeutic approach that uses MAO inhibitors and DA precursors in DA- deficient disorders in which continuous stimulation of the dopaminergic receptors is preferable.
AB - 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 intracellular recordings in vitro. The cellular responses to DA, attributable to the activation of somatodendritic D2/3 autoreceptors, were prolonged and did not completely wash out after pharmacological blockade of both types (A and B) of MAO. On the contrary, depression of the firing 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 caused a short-term prolongation of DA responses, the combined inhibition 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 simultaneous inhibition of MAO and the DA reuptake system. Interestingly, the actions of amphetamine were not clearly augmented by MAO inhibition. From the present data it is concluded that the termination of DA action in the brain is controlled mainly by MAO enzymes. This long- term prolongation of the dopaminergic responses suggests a substitutive therapeutic approach that uses MAO inhibitors and DA precursors in DA- deficient disorders in which continuous stimulation of the dopaminergic receptors is preferable.
KW - cocaine
KW - intracellular recordings
KW - nomifensine
KW - pargyline
KW - substantia nigra
KW - ventral tegmental area
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M3 - Article
C2 - 9065488
AN - SCOPUS:0030903899
VL - 17
SP - 2267
EP - 2272
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7
ER -