Determination of 3-methoxytyramine in rat brain by HPLC with electrochemical detection and its correlation with dopamine function after administration of a monoamine oxidase inhibitor and L-3,4-dihydroxyphenylalanine.

3-Methoxytyramine (3-MT), normally a minor metabolite of 3,4-dihydroxyphenylethylamine (dopamine) in brain, becomes the sole product of metabolism following the administration of a monoamine oxidase (MAO) inhibitor. A simplified reverse-phase HPLC method for 3-MT employing electrochemical detection is fully described. This method has a detection limit of 0.1 microgram/g brain wet weight and is sensitive enough to detect 3-MT in individual brain regions after rats have been pretreated with an MAO inhibitor. Administration of tranylcypromine (TCP, 10 mg/kg) and L-3,4-dihydroxyphenylalanine (L-DOPA) (10-50 mg/kg) produced a dose-dependent linear increase in 3-MT concentrations in the dopaminergic brain regions n. caudatus (r = 0.95; p less than 0.01) and n. accumbens (r = 0.96; p less than 0.01). This treatment also produced a dose-dependent increase in behavioural activity in rats (r = 0.88; p less than 0.01). Furthermore, a good correlation was found between the activity responses of individual rats and the accumulation of 3-MT after TCP/L-DOPA in both n. caudatus (r = 0.76; p less than 0.01) and n. accumbens (r = 0.84; p less than 0.01). These data describe a simple and sensitive HPLC analysis technique for 3-MT and demonstrate that following administration of an MAO inhibitor this metabolite may provide a useful monitor of central dopamine function.