Altered characteristics of striatal [3H]ADTN binding following substantia nigra lesions

The present experiments examined some characteristics of the enhanced striatal [3H]ADTN binding which occurs following substantia nigra lesion. The amount of binding of a fixed concentration of [3H]ADTN was greatly increased. The amount of guanine nucleotide sensitivity increased to an even greater extent than total [3H]ADTN binding. Saturation experiments showed one component of [3H]ADTN binding (KD 7 nM) in intact striata whereas there were two components of binding (KD 9 nM and KD 1 nM) in substantia nigra-lesioned striata. Most of the enhanced binding in substantia nigra-lesioned striata was the higher affinity component. Kainic acid lesion of substantia nigra-lesioned striata caused loss of the enhanced [3H]ADTN binding and the high affinity component of [3H]ADTN binding. These results indicate that following dopaminergic denervation, either the binding characteristics of a single type of dopamine receptor are altered or there is a specific increase in a distinct subtype of dopamine receptor with high agonist affinity and sensitivity to guanine nucleotides.