Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT-107 attenuates the reinstatement of nicotine-seeking behavior in rats

Behav Brain Res. 2014 Nov 1;274:168-75. doi: 10.1016/j.bbr.2014.08.016. Epub 2014 Aug 14.

Abstract

Current smoking cessation pharmacotherapies have modest efficacy, and most smokers relapse within the first few days after a quit attempt. Nicotine withdrawal-induced craving and cognitive impairments predict smoking relapse during abstinence and suggest that cognitive-enhancing drugs may prevent relapse. ABT-089 and ABT-107 are subtype-selective nAChR agonists that improve cognitive performance in laboratory animals. However, there are no studies examining the effects of ABT-089 and ABT-107 on nicotine self-administration and the reinstatement of nicotine-seeking behavior, an animal model of relapse in human smokers. The goal of the present study was to determine the effects of the α4β2*/α6β2* nAChR agonist ABT-089 and the α7 nAChR agonist ABT-107 on nicotine taking and seeking in rats. The effects of acute ABT-089 and ABT-107 pretreatment on nicotine self-administration and reinstatement were tested in male Sprague Dawley rats. Parallel studies of ABT-089 and ABT-107 on sucrose self-administration and reinstatement were tested in separate groups of rats to determine if the effects of these drug treatments generalized to other reinforced behaviors. Nicotine and sucrose self-administration behaviors were not altered following acute administration of ABT-089 (0, 0.12, 1.2 and 12.0mg/kg) or ABT-107 (0, 0.03 and 0.3mg/kg). In contrast, both ABT-089 and ABT-107 pretreatment dose-dependently attenuated nicotine reinstatement. These effects were reinforcer-specific as no effects of ABT-089 or ABT-107 pretreatment on sucrose seeking were noted. Taken together, these findings suggest that ABT-089 and ABT-107 do not affect nicotine consumption, but may reduce the likelihood that a smoking lapse will lead to relapse.

Keywords: Addiction; Relapse; Self-administration; Smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior / drug effects*
  • Indoles / pharmacology*
  • Male
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Nicotinic Agonists / pharmacology*
  • Pyridines / pharmacology*
  • Pyrrolidines / pharmacology*
  • Quinuclidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement Schedule
  • Reward
  • Self Administration
  • Sucrose / administration & dosage

Substances

  • 5-(6-(1-azabicyclo(2,2,2)oct-3-yloxy)pyridazin-3-yl)-1H-indole
  • Indoles
  • Nicotinic Agonists
  • Pyridines
  • Pyrrolidines
  • Quinuclidines
  • Sucrose
  • Nicotine
  • pozanicline