The effects of eticlopride and the selective D3-antagonist PNU 99194-A on food- and cocaine-maintained responding in rhesus monkeys

Renee Claytor, Joshua A. Lile, Michael A. Nader

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The dopamine D3 receptor is mainly expressed in regions of the brain associated with the limbic system. D3 receptor blockade may antagonize cocaine reinforcement while producing less severe extrapyramidal side effects than blockade of D2 receptors. The purpose of the present studies was to evaluate the effects of a selective D3 receptor antagonist and a non-selective D2/D3 receptor antagonist on food- and cocaine-maintained responding under two schedules of cocaine self-administration. Adult male rhesus monkeys were trained to respond under multiple schedules of food (1.0 g pellets) and cocaine (0.01-0.3 mg/kg/injection) presentation. In one experiment (n = 4), the schedule was a fixed-interval (FI) 3-min and a second study (n = 6) was conducted using a second-order fixed-ratio 5 (FI 6-min : S) schedule. The D3 antagonist PNU 99194-A (0.3-3.0 mg/kg), which is 14-fold selective for D3 relative to D2 receptors, or the D2/D3 antagonist eticlopride (0.001-0.03 mg/kg) was administered immediately prior to the experimental session for at least 5 consecutive sessions. Under the multiple FI 3-min schedule of food and cocaine presentation, PNU 99194-A and eticlopride decreased food- and cocaine-maintained responding in a dose-dependent manner and irrespective of cocaine dose. Under the multiple second-order schedule of food and cocaine presentation, at least one dose of PNU 99194-A and eticlopride decreased cocaine- and food-maintained responding. These findings indicate that PNU 99194-A can decrease operant responding in monkeys, but not in a manner that would suggest selectivity of cocaine- over food-maintained responding. Future studies with more selective D3 antagonists are needed to better address the role of this receptor subtype in cocaine addiction.

Original languageEnglish
Pages (from-to)456-464
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume83
Issue number3
DOIs
StatePublished - Mar 2006

Bibliographical note

Funding Information:
The authors thank Tonya Moore Calhoun, Jennifer Sandridge, Clifford Hubbard and Susan Nader for excellent technical assistance, Dr. William W. Stoops for statistical consultation and Dr. Paul W. Czoty for comments on an earlier version of this manuscript. The research was supported by National Institute on Drug Abuse (NIDA) research grant DA 12460 (MAN) and NIDA Training Grant (DA 16455). These experiments represent a portion of the work conducted by R. Claytor as part of her dissertation research.

Keywords

  • Dopamine D receptor antagonist
  • Eticlopride
  • PNU 99194-A
  • Rhesus monkey
  • Self-administration

ASJC Scopus subject areas

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

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