Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors

Summary The treatment of Sprague-Dawley rats with monoamine oxidase (MAO) inhibitors (pargyline, tranylcypromine) profoundly affects dopamine (DA) and norepinephrine (NE) metabolism in the brain. In these rats injection of L-dopa led to large increases in norepinephrine (NE), normetanephrine (NMN) and 3-methoxytyramine (3-MT) in brain tissues. The response of MAO-inhibited rats to L-dopa contrasted sharply with those not treated with the MAO inhibitor; the latter showed no change in NE, NMN and 3-MT after similar administration of L-dopa. The increase of NE in pargyline-treated rats correlated closely with that of DA in the hypothalamus and in the brain stem. This response was greatly diminished in rats previously treated with the neurotoxin 6-hydroxydopamine, but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine. This suggests that noradrenergic neurons were the origin of the NE response. The NMN and 3-MT increases occurring only in the rats treated with a MAO inhibitor were highly correlated. The results suggested that MAO inhibitor may affect entry of DA into catecholaminergic storage where NE synthesis takes place and from where DA is released.