Intracerebral infusion of DOPAC decreases striatal dopamine.
The purpose of this study was to determine whether elevated levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine (DA) in the brain, could decrease the DA content in the striatum. Levels of DA were determined by high pressure liquid chromatography with electrochemical detection (HPLC-EC) in the striatum of male rats 24 h following a single intracerebral administration of DOPAC into the right striatum. DOPAC at 16.8 micrograms reduced the DA content of the infused side by 17%, p = 0.01. In contrast, infusion of 1.68 micrograms of DOPAC or the vehicle had no effect on striatal DA levels. Coapplication of the antioxidant, ascorbic acid, at 0.2 mg/ml with 16.8 micrograms of DOPAC prevented the decrease in DA content. Furthermore, infusion of 18.2 micrograms of homovanillic acid (HVA), the product of DOPAC methylation, had no effect on striatal DA. These results indicate that DOPAC may undergo autoxidation in vivo to produce neurotoxic species which may result in reduction of striatal DA. Formation of such an autoxidation product(s) of endogenous DOPAC was verified in the extracellular fluid of striatal slices in vitro.
Shiekhattar
R
R
University of Kansas, Department of Biochemistry, Lawrence 66045.
Ghasemzadeh
M B
MB
Adams
R N
RN
D015102:3,4-Dihydroxyphenylacetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid