Acute perfusion of BMAA in the rat's striatum by in vivo microdialysis.
The present study is concerned with the hypothetical toxicity of beta-N-methylamino-L-alanine (BMAA), a compound that has been hypothesized to produce amyotrophic lateral sclerosis/Parkinson-dementia complex. We have used the microdialysis technique to perfused different concentrations of BMAA in the rat's striatum 24h after the implantation of a microdialysis probe (day 1). BMAA perfusion produced a dose-response increase in the extracellular output of dopamine. Forty-eight hours after implantation of the probe (day 2), we have perfused MPP+ 1 mM to check the integrity of the dopaminergic terminals present around the cannula. Only the highest concentration of BMAA studied, 50mM, produced a clear decrease in the extracellular output of dopamine after MPP+ perfusion. However, this decrease was very similar, even smaller, to that obtained in a previous study carried out by us with MPP+ 1 mM, a dose much lower than that used for BMAA. Our model to study toxicity in the striatal dopaminergic terminal did not show that acute perfusion of BMAA at high doses produces a clear damage to the dopaminergic terminals.
Santiago
M
M
Departamento de Bioquímica, Facultad de Farmacia, Sevilla, Spain. msantiago@us.es
Matarredona
E R
ER
Machado
A
A
Cano
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002560:Cerebrovascular Circulation; D002851:Chromatography, High Pressure Liquid; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D017551:Microdialysis; D017072:Neostriatum / Q000098:blood supply / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; C001824:beta-N-methylamino-L-alanine; D004298:Dopamine; D006719:Homovanillic Acid