Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats

J Neurochem. 1986 Apr;46(4):1277-82. doi: 10.1111/j.1471-4159.1986.tb00650.x.

Abstract

A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and the area was perfused with Ringer solution while the animals were unanesthetized after at least 3 days following surgery. Concentrations of the metabolites of 3,4-dihydroxyphenylethylamine (DA) and 5-hydroxytryptamine (5-HT) in the perfusate were determined by HPLC with electrochemical detection. Levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perfusate significantly decreased after pargyline administration (50 mg/kg i.p.), which may inhibit not only monoamine oxidase (MAO)-B but also MAO-A in these high doses. The level of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) also decreased after pargyline treatment, although change in the relative level of 5-HIAA was less than that of DOPAC or HVA. To clarify the mechanisms for the metabolism of monoamines in rat striatum, highly specific MAO-A and -B inhibitors were used in the following experiments. Treatment with l-deprenyl (10 mg/kg), a specific inhibitor for MAO-B, did not cause any statistically significant change in DOPAC, HVA, and 5-HIAA levels. No significant change was found in rat striatal homogenates at 2 h after the same treatment with l-deprenyl. In contrast, low-dose treatment (1 mg/kg) with clorgyline, a specific inhibitor for MAO-A, caused a significant decrease in levels of these three metabolites in both the perfusates and tissue homogenates. In addition to the above three metabolites, the level of 3-methoxytyramine, which is an indicator of the amount of DA released, greatly increased after treatment with a low dose (1 mg/kg) of clorgyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Chromatography, High Pressure Liquid
  • Clorgyline / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology*
  • Dialysis
  • Dopamine / analogs & derivatives
  • Dopamine / metabolism*
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Pargyline / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism*

Substances

  • Monoamine Oxidase Inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Pargyline
  • Monoamine Oxidase
  • 3-methoxytyramine
  • Clorgyline
  • Dopamine
  • Homovanillic Acid