The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions

Int J Neuropsychopharmacol. 2006 Oct;9(5):585-602. doi: 10.1017/S1461145706006560. Epub 2006 Aug 31.

Abstract

Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Area Under Curve
  • Association Learning / drug effects
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Conditioning, Operant / drug effects*
  • Cues
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Motor Activity / drug effects
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Nitriles / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Reward*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Dopamine Antagonists
  • Nicotinic Agonists
  • Nitriles
  • SB 277011
  • Tetrahydroisoquinolines
  • Nicotine