Early toxic effect of 6-hydroxydopamine on extracellular concentrations of neurotransmitters in the rat striatum: an in vivo microdialysis study.
The early effects of 6-OHDA as a Parkinsonian model in rodents are relevant since pharmacological and toxicological points of view, as they can explain the acute and chronic deleterious events occurring in the striatum. In this study, we focused our attention on the neurochemical and motor dysfunction produced after a pulse infusion of 6-OHDA, paying special attention to the capacity of this molecule to induce neurotransmitter release and behavioural alterations. Extracellular levels of dopamine, serotonin, norepinephrine, glutamate, glutamine, aspartate, glycine and GABA were all assessed in striatal dialysates in freely moving rats immediately after exposed to a single pulse of 6-OHDA in dorsal striatum, and major behavioural markers of motor alterations were simultaneously explored. Enhanced release of dopamine, serotonin and norepinephrine was found immediately after 6-OHDA pulse. Delayed glutamate and glycine release were detected and a biphasic effect on GABA was observed. Mostly serotonin and dopamine outflow, followed by glutamate, correlated with wet dog shakes and other behavioural qualitative alterations. Early dopamine release, accompanied by other neurotransmitters, can generate an excitatory environment affecting the striatal neurons with immediate consequences for behavioural performance. In turn, these changes might be accounting for later features of toxicity described in this model.
Tobón-Velasco
Julio César
JC
Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, México D.F., Mexico.
Silva-Adaya
Daniela
D
Carmona-Aparicio
Liliana
L
García
Esperanza
E
Galván-Arzate
Sonia
S
Santamaría
Abel
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018377:Neurotransmitter Agents; D016627:Oxidopamine