Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by D2 autoreceptors

Su Jin Yi, Kenneth M. Johnson

Research output: Contribution to journalArticle

62 Scopus citations


The effect of repeated administration of cocaine on presynaptic D2 autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca2+-evoked 3H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D2 antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.

Original languageEnglish (US)
Pages (from-to)457-461
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Issue number3
StatePublished - Jul 1990


  • Behavioral sensitization
  • Chronic cocaine
  • DA autoreceptor
  • DA release

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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