title: Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine.
abstract: Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a response-independent manner only on nicotine sessions. On intervening test days, rats were pretreated with iptakalim (10, 30, 60 mg/kg, IP). Results revealed that iptakalim attenuated nicotine-evoked responding controlled by the nicotine stimulus in a dose-dependent manner. In a separate study, the impact of iptakalim on the reinforcing effects of nicotine was investigated by training rats to lever-press to self-administer nicotine (0.01 mg/kg/infusion) [Dosage error corrected]. Results revealed that pretreatment with iptakalim (1, 3, 6 mg/kg, IV) decreased nicotine intake (i.e., less active lever responding). Neither behavioral effect was due to a non-specific motor effect of iptakalim, nor to an ability of iptakalim to inhibit DA transporter (DAT) or serotonin transporter (SERT) function. Together, these finding support the notion that iptakalim may be an effective pharmacotherapy for increasing smoking cessation and a better understanding of its action could contribute to medication development.
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: S
authors.initials: S
authors.lastname: Charntikov
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: N
authors.initials: N
authors.lastname: Swalve
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: S
authors.initials: S
authors.lastname: Pittenger
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: K
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: S
authors.initials: S
authors.lastname: Schepers
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Hadlock
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Fleckenstein
authors.affiliation: Jiangsu Province Key Lab of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE 68588-0308, USA. Electronic address: rbevins1@unl.edu.
authors.forename: R A
authors.initials: RA
authors.lastname: Bevins
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D006040:Goals; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011437:Propylamines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012701:Serotonin / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D049990:Membrane Transport Modulators; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D018722:Nicotinic Agonists; D011437:Propylamines; D014316:Tritium; D012701:Serotonin; D009538:Nicotine; D004298:Dopamine
keywords: Drug discrimination; Interoceptive stimulus; Iptakalim; Nicotine dependence; Pavlovian conditioning; Self-administration; Smoking; Tobacco
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