title: Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT-107 attenuates the reinstatement of nicotine-seeking behavior in rats.
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.
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, TRL Building, Rm 2214, Philadelphia, PA 19104, United States.
authors.forename: Alycia M
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, TRL Building, Rm 2214, Philadelphia, PA 19104, United States.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Arreola
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, TRL Building, Rm 2214, Philadelphia, PA 19104, United States.
authors.forename: Blake A
authors.initials: BA
authors.lastname: Kimmey
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, TRL Building, Rm 2214, Philadelphia, PA 19104, United States. Electronic address: hschmidt@mail.med.upenn.edu.
authors.forename: Heath D
authors.initials: HD
authors.lastname: Schmidt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
chemical_list: C552256:5-(6-(1-azabicyclo(2,2,2)oct-3-yloxy)pyridazin-3-yl)-1H-indole; D007211:Indoles; D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D011812:Quinuclidines; D013395:Sucrose; D009538:Nicotine; C108326:pozanicline
keywords: Addiction; Relapse; Self-administration; Smoking