5-HT3 receptor antagonists block cocaine-induced locomotion via a PCPA-sensitive mechanism

Adena L. Svingos, Robert Hitzemann

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

We report results in rats pretreated with (±)-zacopride (0.03 mg/kg, IP), ICS 205-930 (0.1 mg/kg, IP), and MDL 72222 (1.0 mg/kg, IP) 15 min before challenge with (-)-cocaine (10.0 mg/kg, IP). At a dose of 10 μg/kg, zacopride significantly inhibited (approximately 50%) cocaine-induced locomotion. We also investigated whether or not 5-hydroxytryptamine3 (5-HT3) antagonists block the cocaine binding site on the dopamine transporter and/or affect the ability of dopamine to regulate this binding site. In well-washed striatal membranes, neither zacopride nor ICS 205-930 (10-9-10-5 M) inhibited [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane ([3H]WIN 35,428) (0.3 nM) binding. Furthermore, neither of these compounds affected the ability of dopamine to block WIN 35,428 binding. To determine if 5-HT is required for the 5-HT3 antagonist effect, we examined the interaction between cocaine and zacopride in rats pretreated with p-chlorophenylalanine (PCPA) (3 days × 100 mg/kg/day). PCPA pretreatment shifted the cocaine dose-response curve to the right and blocked the ability of zacopride to reverse cocaine-induced activity.

Original languageEnglish (US)
Pages (from-to)871-879
Number of pages9
JournalPharmacology, Biochemistry and Behavior
Volume43
Issue number3
DOIs
StatePublished - Nov 1992

Keywords

  • 5-HT antagonists
  • Behavior
  • Cocaine
  • Dopamine transporter
  • PCPA
  • Rat
  • Serotonin

ASJC Scopus subject areas

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

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