D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity

Concepció Marin, Sotirios A. Parashos, Vasiliki Kapitzoglou-Logothetis, Antonella Peppe, Thomas N. Chase

Research output: Contribution to journalArticlepeer-review

Abstract

The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominatly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes.

Original languageEnglish
Pages (from-to)195-200
Number of pages6
JournalPharmacology, Biochemistry and Behavior
Volume45
Issue number1
DOIs
Publication statusPublished - 1993

Keywords

  • Behavioral supersensitivity
  • Catalepsy
  • Dopamine receptor interactions
  • Neuroleptics
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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