Semi-chronic increase in striatal level of 3,4-dihydroxyphenylacetaldehyde does not result in alteration of nigrostriatal dopaminergic neurones.
This work was carried out to evaluate the potential in vivo toxicity of 3,4-dihydroxyphenylacetaldehyde (DOPAL), an aldehyde formed from dopamine by monoamine oxidase (MAO) that is oxidised mainly to 3,4-dihydroxyphenylacetic acid (DOPAC) by brain aldehyde dehydrogenases (ALDH). In this study, male Sprague-Dawley rats were treated with levodopa (L-dopa)-benserazide, which increases DOPAL production by MAO, and disulfiram, an irreversible inhibitor of ALDH, which reduces the formation of DOPAC from DOPAL. An acute systemic intraperitoneal (i.p.) injection of 100 mg/kg disulfiram and L-dopa-benserazide (100 mg/kg + 25 mg/kg, 24 hr later) significantly increased DOPAL striatal level. A 30-day treatment with disulfiram (100 mg/kg i.p., once every 2 days) and L-dopa-benserazide (100 mg/kg + 25 mg/kg, two times/day) did not affect either indexes used to assess integrity of the nigrostriatal dopaminergic neurones (i.e., the striatal content in dopamine and binding to the vesicular monoamine transporter on striatal membranes). These results do not evidence any deleterious effect of DOPAL and argue against toxicity of L-dopa therapy.
Legros
Hélène
H
Unité de Neuropsychopharmacologie Expérimentale, UMR 6036 CNRS, IFRMP N 23, Rouen, France.
Janin
François
F
Dourmap
Nathalie
N
Bonnet
Jean-Jacques
JJ
Costentin
Jean
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004221:Disulfiram / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; C007430:3,4-dihydroxyphenylacetaldehyde; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram; D004298:Dopamine