In vivo blockade of dopaminergic receptors from different rat brain regions by classical and atypical neuroleptics

There is no correlation between the selective regional stimulation of dopamine turnover after neuroleptics and the in vivo blockade of postsynpatic dopaminergic receptors in the striatum or in the limbic system, respectively.

Abstract

The effect of haloperidol, chlorpromazine, clozapine, benzamides (sulpiride and isosulpride), 6-chloropyrimidines (mezilamine, UK 177) on the in vivo binding of [3H]spiroperidol to striatum, tuberculum olfactorium, frontal cortex and cerebellum in the rat brain was investigated. Since these neuroleptics of various chemical classes were able to prevent the selective retention of [3H]spiroperidol in the striatum and tuberculum olfactorium without modifying the level in the cerebellum, it has been assumed that [3H]spiroperidol is a suitable ligand to label dopaminergic receptors in the living animal. All the neuroleptics (except the benzamides) were able to displace [3H]spiroperidol from its receptors in the frontal cortex, suggesting a serotoninergic component in neuroleptic binding sites. Classical neuroleptics (haloperidol, chlorpromazine, UK 177) or atypical neuroleptics (clozapine, sulpiride, isosulpride, mezilamine) did not induce a selective blockade of dopaminergic receptors in the striatum or in the limbic system, respectively. These results indicate that there is no correlation between the selective regional stimulation of dopamine turnover after neuroleptics and the in vivo blockade of postsynpatic dopaminergic receptors.