Inhibition of brain MAO-A and animal behaviour induced by p-hydroxyamphetamine.
Intra- and extra-synaptosomal activity of monoamine oxidase-A (MAO-A) and -B (MAO-B), dopamine (DA) and its main metabolites were examined to clarify the mechanism of action(s) of p-hydroxyamphetamine (p-OHA) in animal behaviour mediated by central dopaminergic systems. Intrasynaptosomal DA was oxidized by MAO-A and MAO-B and this oxidation is inhibited by p-OHA. The inhibition is due to two effects: 1) uptake of DA is inhibited by p-OHA, and 2) p-OHA also inhibits intrasynaptosomal oxidation of DA by MAO-A and MAO-B. The inhibition of oxidation by MAO-A is predominant. Administration (ICV) of 80 and 160 micrograms p-OHA to mice, doses that cause various behavioural, significantly reduced striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, but greatly increased 3-methoxytyramine, without significantly changing homovanillic acid (HVA). The release of DA and blockade of DA uptake into dopaminergic neurons by p-OHA, together with preferential inhibition of the DA metabolizing enzyme, MAO-A, may contribute to p-OHA-induced behaviour mediated by the central dopaminergic systems.
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Y
Y
Arai
S K
SK
Kim
H
H
Kinemuchi
T
T
Tadano
K
K
Oyama
N
N
Satoh
K
K
Kisara
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D016548:Prosencephalon / Q000201:enzymology*; D012016:Reference Values; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology*; D010136:p-Hydroxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D008995:Monoamine Oxidase; D010136:p-Hydroxyamphetamine; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid