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

Su Jin Yi, Kenneth M. Johnson

Research output: Contribution to journalArticlepeer-review

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
Externally publishedYes


  • 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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