Effects of SCH-23390 on dopamine D1 receptor occupancy and locomotion produced by intraaccumbens cocaine infusion

Janet Neisewander, Rita A. Fuchs, Laura E. O'Dell, Taline V. Khroyan

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

This study examined the effects of both systemic and intraaccumbens administration of SCH-23390 in rats on dopamine D1 receptor occupancy and on locomotor activity produced by intraaccumbens infusion of cocaine. In experiment 1, rats received SCH-23390 (0-1 mg/kg, IP) 15 minutes prior to intraaccumbens infusion of cocaine (0 or 100 μg/side). In experiment 2, rats received coinfusion of SCH-23390 (0-1 μg/side) and cocaine (0 or 100 μg/side) into the nucleus accumbens (NAc). After behavioral testing, receptors occupied by SCH-23390 were quantified by injecting animals with their respective dose of SCH-23390, followed by a systemic injection of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Receptors occupied by SCH-23390, and therefore protected from EEDQ- induced inactivation, were quantified from autoradiograms of sections labeled with 3H-SCH-23390. Systemic administration of SCH-23390 dose-dependently (0.1-1.0 mg/kg) reversed cocaine-induced locomotion and occupied 72-100% of D1-like receptors in the anterior NAc. D1 receptor occupancy following systemic administration of SCH-23390 was evident as an inverted U-shaped, dose-dependent change, with the greatest occupancy observed at the intermediate dose of 0.3 mg/kg. Intraaccumbens infusion of SCH-23390 did not alter cocaine-induced locomotor activity despite occupying 40-60% of D1-like receptors in the anterior NAc core and shell. The findings that systemic, but not intraaccumbens, administration of SCH-23390 potently reversed locomotion produced by intraaccumbens cocaine infusion suggest that stimulation of D1 receptors in regions other than the NAc is involved in locomotion produced by intraaccumbens infusion of cocaine, and that stimulation of D1 receptors in the NAc is not necessary for this behavior.

Original languageEnglish (US)
Pages (from-to)194-204
Number of pages11
JournalSynapse
Volume30
Issue number2
DOIs
StatePublished - Oct 1 1998

Keywords

  • Caudate-putamen
  • Cocaine
  • Dopamine D1 recep- tors
  • Localization
  • Locomotor activity
  • N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquino- line
  • Nucleus accumbens
  • Receptor autoradiography
  • Receptor occupancy
  • SCH-23390
  • Sniffing

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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