The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons.

The nigrostriatal dopaminergic pathway was selected as a model system to determine the form (i.e., type A or B) of monoamine oxidase (MAO) present within central dopamine (DA)-containing neurons. The preferential accumulation and subsequent intraneuronal deamination of [14C]DA by striatal synaptosomes was examined in synaptosomal-rich homogenates obtained from rats previously treated (i.v.) with graded doses of either clorgyline or deprenyl. To confirm the selective MAO inhibitor properties of clorgyline or deprenyl, type A and B MAO activity was simultaneously assayed in striatal aliquots of the same tissue pool. The selective inhibition of type A MAO by clorgyline was associated wih a decline in the synaptosomal deamination of [14C]DA. These results were further substantiated by experiments performed on the synaptosomal deamination of [3H]DA, newly synthetized from [3H]tyrosine in the presence of either clorgyline or deprenyl. The deamination of newly synthetized [3H]DA was reduced by the selective inhibition of type A MAO. Finally, the destruction of DA-containing nigrostriatal neurons by the stereotaxic administration of 6-hydroxydopamine produced a selective reduction in the type A MAO activity in the striatum ipsilateral to the 6-hydroxydopamine-injected substantia nigra. A high correlation was obtained between the size of the DA-containing neuronal lesion and the reduction in type A MAO activity. No reduction in type B MAO activity was observed. These results strongly indicate the presence of the type A form of MAO within nigrostriatal dopaminergic neurons of the rat brain.