Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors.
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.
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Laboratory of the Autonomic Nervous System, University of Montreal, Quebec, Canada.
Angers
M
M
Duhaime
J
J
Kuchel
O
O
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008996:Monoamine Oxidase Inhibitors; D009647:Normetanephrine; D007980:Levodopa; D010293:Pargyline; C001746:3-methoxytyramine; D004298:Dopamine; D009638:Norepinephrine