Dopamine D2 and D3 receptor preferring antagonists differentially affect striatal dopamine release and metabolism in conscious rats

Eur J Pharmacol. 1994 Aug 22;261(3):327-31. doi: 10.1016/0014-2999(94)90125-2.

Abstract

Classical neuroleptic drugs with high affinity for dopamine D2 receptors in comparison to D3 ones (haloperidol, thioproperazine and spiperone) administered i.p. acutely (0.2, 0.2 and 0.07 mg/kg, respectively) induced a pronounced increase in the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) and only a modest rise in that of dopamine in the dorsal striatum of conscious rats studied by transcerebral microdialysis. Atypical neuroleptics, clozapine and thioridazine (both 20 mg/kg), demonstrating relatively higher affinity for dopamine D3 receptor than typical ones, as well as the dopamine D3 receptor and autoreceptor preferring antagonists, cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n- propylamino)tetralin HCl ((+)-UH232) and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-propylamino)tetralin HCl ((+)-AJ76) (both 14 mg/kg), were equally effective or even more potent in increasing dopamine release than DOPAC. It is concluded that the dopamine D2/D3 receptor relative potencies of typical and atypical neuroleptics appear to correspond to their ability to affect preferentially dopamine metabolism or release in rat dorsal striatum in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Antipsychotic Agents / pharmacology
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology*
  • Male
  • Microdialysis
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D3

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • 3,4-Dihydroxyphenylacetic Acid
  • Dopamine