Differential regulation of glutamate, aspartate and gamma-aminobutyrate release by N-methyl-D-aspartate receptors in rat striatum after partial and extensive lesions to the nigro-striatal dopamine pathway
J. Abarca et G. Bustos, Differential regulation of glutamate, aspartate and gamma-aminobutyrate release by N-methyl-D-aspartate receptors in rat striatum after partial and extensive lesions to the nigro-striatal dopamine pathway, NEUROCHEM I, 35(1), 1999, pp. 19-33
The in vivo microdialysis methodology was used to assess the effect of N-me
thyl-D-aspartate (NMDA) receptor ligands on glutamate (GLU), aspartate (ASP
) and gamma-aminobutyrate (GABA) extracellular levels in the striatum of an
aesthetized rats, after damage to the dopamine (DA) nigrostriatal pathway b
y injections of different doses of 6-hydroxydopamine (6-OH-DA) seven days e
arlier. The 6-OH-DA treated rats were divided into two groups, correspondin
g to animals with 20-80% (partial) and 85-99% (extensive) striatal DA tissu
e depletion, respectively. In rats with partial DA depletion, the striatal
extracellular ASP levels significantly increased after intrastriatal dialys
is perfusion with MK-801 (100 mu M), an antagonist of NMDA receptors. In ad
dition, a change in the pattern of local NMDA (500 mu M)- induced efflux of
ASP was observed in the striatum of these rats. However, in these partiall
y DA-depleted striata no changes were found in basal extracellular levels o
f GLU, ASP and GABA or in NMDA- and MK-801-mediated effluxes of GLU and GAB
A relative to striata from sham rats. In contrast, rats with extensive stri
atal DA depletion exhibited a significant increase in ASP and GABA extracel
lular striatal levels, after intrastriatal dialysis perfusion with NMDA. In
addition, the MK-801-mediated stimulation of extracellular ASP levels was
accentuated along with the appearance of a MK-801 mediated increase in extr
acellular striatal GLU. Finally, basal extracellular levels of ASP, but not
of GLU and GABA, were found to increase in extensive DA-depleted striata w
hen compared to sham and partially DA-depleted striata. Thus, a differentia
l regulation of basal and NMDA receptor-mediated release of transmitter ami
no acids occur seven days after partial and extensive DA-depleted striatum
by 6-OH-DA-induced lesions of the nigrostriatal DA pathway.
These findings may have implications as regards the participation of NMDA r
eceptors in the compensatory mechanisms associated with the progress of Par
kinson's disease, as well as in the treatment of this neurological disorder
. (C) 1999 Elsevier Science Ltd. All rights reserved.