DA2/NT receptor balance in the mesostriatal and mesolimbocortical systems after chronic treatment with typical and atypical neuroleptic drugs

Brain Res. 1990 Nov 5;532(1-2):140-5. doi: 10.1016/0006-8993(90)91753-4.

Abstract

Typical and atypical neuroleptic drugs show several clinical and behavioral effects, possibly related to the different anatomical sites of the action in the mesolimbocortical or mesostriatal dopaminergic systems. Because of the interaction between dopamine (DA) and neurotensin (NT) in the target areas of these systems, and in order to study if the different action of typical and atypical neuroleptic drugs could be related to a modification of the DA/NT balance, we investigated DA2 and NT receptor modifications--by means of quantitative receptor autoradiography--after chronic treatment with low dosage of haloperidol, chlorpromazine, thioridazine and clozapine. We described a decrease of NT receptor density in the target areas of the mesolimbocortical system produced by all the treatments. This effect does not match with DA2 receptor modifications. On the contrary, the block of DA transmission obtained by high dosage of haloperidol induces an increase of NT receptor density. Our results further demonstrate the regulation of NT transmission by DAergic drugs.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Autoradiography
  • Brain / drug effects*
  • Brain / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Chlorpromazine / pharmacology
  • Clozapine / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Haloperidol / pharmacology
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Male
  • Neurotensin*
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Neurotensin
  • Receptors, Neurotransmitter / drug effects*
  • Receptors, Neurotransmitter / metabolism
  • Thioridazine / pharmacology
  • Time Factors

Substances

  • Antipsychotic Agents
  • Receptors, Dopamine
  • Receptors, Neurotensin
  • Receptors, Neurotransmitter
  • Neurotensin
  • Clozapine
  • Haloperidol
  • Thioridazine
  • Chlorpromazine