Supersensitivity time course of dopamine antagonist binding after nigrostriatal denervation: evidence for early and drastic changes in the rat corpus striatum.

The sensitivity of the [3H]haloperidol binding technique can be greatly increased by focusing tissue sampling on striatal regions where dopaminergic innervation is the richest. Such sampling is provided from pooled microdiscs punched out of 8 serial 500 micrometer thick sections of the rat brain. With these conditions, the density of receptor sites (Bmax) was found to be twice that of the whole striatum, without modification of the apparent dissociation constant (Kd) and of the Hill's slope. Such a procedure applied to rats with complete 6-hydroxydopamine-induced unilateral nigrostriatal lesions showed a moderate decrease in Bmax in the lesioned side up to 6 days after surgery, whereafter the value of Bmax increased progressively up to the thirtieth day, being then 160% over the control value. Conversely, the apparent Kd decreased significantly from the second to the sixth day postsurgery in the lesioned side, and then increased moderately up to the tenth day and drastically from the twenty-first to the thirtieth day. No change was observed in the corresponding intact side. The modifications appeared chronologically compatible with those corresponding to the behavioral denervation supersensitivity, evidencing drastic binding changes as compared with the whole striatum. The unexpected variations in Kd observed were well correlated with those in Bmax, suggesting that the new available binding sites might be of lower affinity. In the light of all these results, a hypothetical model is proposed.