LOCALIZATION OF HIGH-AFFINITY [3-H]GLIBENCLAMIDE BINDING-SITES WITHINTHE SUBSTANTIA-NIGRA ZONA RETICULATA OF THE RAT-BRAIN

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.