Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in drug self-administration and drug discrimination in rats

Gregory T. Collins, Paul Butler, Chris Wayman, Sian Ratcliffe, Paul Gupta, Geoffrey Oberhofer, S. Barak Caine

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Dopamine D3-preferring agonists are commonly used to treat Parkinson's disease and restless leg syndrome; however, laboratory animal studies suggest that they may possess a moderate abuse potential. These studies aimed to compare the highly selective, full D 3 agonist PF-592,379 to the less selective D 3 agonist 7-OH-DPAT, and the indirect dopamine agonist cocaine in drug self-administration and discrimination assays. Although rats readily acquired high rates of fixed ratio (FR)1 responding for cocaine, experimentally naive rats failed to acquire responding when 7-OH-DPAT or PF-592,379 was made available during an 18-session acquisition period. Cocaine also maintained dose-dependent levels of responding when available under a FR5 or a progressive ratio (PR) schedule of reinforcement. Although 7-OH-DPAT maintained modest levels of responding when substituted under a FR5, it failed to maintain significant levels of PR responding. PF-592,379 maintained saline-like rates of responding when substituted under FR5 or PR schedules of reinforcement. Similar behavioral profiles were observed in cocaine discrimination assays, with 7-OH-DPAT partially substituting for cocaine, and PF-592,379 producing saline-like effects over a wide range of doses. Together, the results of these studies predict that highly selective D 3 agonists, such as PF-592,379, will have low abuse potential in humans.

Original languageEnglish (US)
Pages (from-to)280-291
Number of pages12
JournalBehavioural pharmacology
Volume23
Issue number3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Cocaine
  • Dopamine D2
  • Dopamine D3
  • Drug discrimination
  • Drug self-administration
  • PF-592,379
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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