Chronic haloperidol does not alter agonist affinity for dopamine receptors in vitro

Agonist competition for [3H]spiperone binding to striatal dopamine D2 receptors was studied in rats rendered supersensitive by chronic treatment with haloperidol. The classical dopamine agonist (-)-N-n-propylnorapomorphine displaced [3H]spiperone biphasically, with IC50 values of 0.5 and 140 nM for the high and low affinity components, respectively. Neither the relative density nor the affinity of either site for (-)-N-propylnorapomorphine was affected by chronic haloperidol treatment. On the other hand, the novel agonist EMD 23 448 displaced [3H]spiperone monophasically. Although this agent only displays potent dopaminergic agonism in supersensitive animals, chronic treatment with haloperidol likewise did not alter the affinity of this drug for [3H]spiperone binding sites. The results suggest that the enhanced in vivo potency of certain agonists in supersensitive animals is probably not mediated by changes in D2 receptor affinity.