Ga. Hicks et al., LOCALIZATION OF HIGH-AFFINITY [3-H]GLIBENCLAMIDE BINDING-SITES WITHINTHE SUBSTANTIA-NIGRA ZONA RETICULATA OF THE RAT-BRAIN, Neuroscience, 61(2), 1994, pp. 285-292
The rat substantia nigra zona reticulata contains a high density of bi
nding sites for glibenclamide, an adenosine triphosphate-sensitive pot
assium channel inhibitor, but the precise location of glibenclamide bi
nding sites within this area has not previously been examined. By comb
ining neurochemical lesion and autoradiographical studies we have show
n that high affinity [H-3]glibenclamide binding sites are located on s
triatonigral terminals. Unilateral injections of 6-hydroxydopamine int
o the medial forebrain bundle or of quinolinic acid into the striatum
were performed in anaesthetized adult rats to lesion the nigrostriatal
and striatonigral pathways respectively. Autoradiography was performe
d on coronal sections of midbrain with [H-3]glibenclamide, [H-3]YM-091
51-2 (dopamine D-2 receptor antagonist) and [H-3]SCH 23390 (dopamine D
-1 receptor antagonist) at three rostrocaudal levels of the substantia
nigra. Under the conditions of the incubation [H-3]glibenclamide bind
s primarily to the high affinity site. Following the 6-hydroxydopamine
nigrostriatal lesion, D-2 receptor binding was reduced (by up to 67%)
on the lesioned side at all three levels of the substantia nigra wher
eas D-1 receptor and glibenclamide binding were not significantly affe
cted. In contrast, following striatonigral pathway lesion with quinoli
nic acid D-2 receptor binding was unchanged on the lesioned side, but
both D-1 receptor and glibenclamide binding were reduced at all three
levels (by up to 85% and 63% in the area of maximum lesion, respective
ly). In adjacent sections, the pattern of D-1 binding loss was closely
paralleled by the loss of glibenclamide binding. These results demons
trate that the high affinity glibenclamide binding sites of the substa
ntia nigra zona reticulata are, at least in part, located on the termi
nals of striatonigral projection neurons.