PG01037, a novel dopamine D3 receptor antagonist, inhibits the effects of methamphetamine in rats

Amanda E. Higley, Krista Spiller, Peter Grundt, Amy Hauck Newman, Stephen W. Kiefer, Zheng Xiong Xi, Eliot L. Gardner

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Our previous studies have shown that the selective dopamine D3 receptor antagonists SB-277011A or NGB 2904 significantly attenuate cocaine self-administration under a progressive-ratio reinforcement schedule and cocaine-, methamphetamine- or nicotine-enhanced brain stimulation reward. However, the poor bioavailability of SB-277011A has limited its potential use in humans. In the present study, we investigated the effects of the novel D 3 receptor antagonist PG01037 on methamphetamine self-administration, methamphetamine-associated cue-induced reinstatement of drug seeking and methamphetamine-enhanced brain stimulation reward. Rats were allowed to intravenously self-administer methamphetamine under fixed-ratio 2 and progressive-ratio reinforcement conditions, and then the effects of PG01037 on methamphetamine self-administration and cue-induced reinstatement were assessed. Additional groups of rats were trained for intracranial electrical brain stimulation reward and the effects of PG01037 and methamphetamine on brain stimulation reward were assessed. Acute intraperitoneal administration of PG01037 (3, 10, 30 mg/kg) failed to alter methamphetamine or sucrose self-administration under fixed-ratio 2 reinforcement, but significantly lowered the break-point levels for methamphetamine or sucrose self-administration under progressive-ratio reinforcement. In addition, PG01037 significantly inhibited methamphetamine-associated cue-triggered reinstatement of drug-seeking behavior and methamphetamine-enhanced brain stimulation reward. These data suggest that the novel D3 antagonist PG01037 significantly attenuates the rewarding effects as assessed by progressive-ratio self-administration and brain stimulation reward, and inhibits methamphetamine-associated cue-induced reinstatement of drug-seeking behavior These findings support the potential use of PG01037 or other selective D3 antagonists in the treatment of methamphetamine addiction.

Original languageEnglish (US)
Pages (from-to)263-273
Number of pages11
JournalJournal of Psychopharmacology
Volume25
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • D3 receptor
  • PG01037
  • brain reward
  • brain-stimulation reward
  • cue-induced reinstatement
  • methamphetamine
  • self-administration

Fingerprint Dive into the research topics of 'PG01037, a novel dopamine D3 receptor antagonist, inhibits the effects of methamphetamine in rats'. Together they form a unique fingerprint.

Cite this