Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine

S. Charntikov, N. Swalve, S. Pittenger, K. Fink, S. Schepers, G. C. Hadlock, A. E. Fleckenstein, G. Hu, Ming Li, Rick A Bevins

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Iptakalim is an ATP-sensitive potassium channel opener, as well as an α 4 β 2 -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 (0.03 mg/kg/infusion). 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.

Original languageEnglish (US)
Pages (from-to)138-144
Number of pages7
JournalNeuropharmacology
Volume75
DOIs
StatePublished - Jan 1 2013

Fingerprint

Self Administration
Nicotine
N-(1-methylethyl)-1,1,2-trimethylpropylamine
KATP Channels
Tobacco Use Disorder
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Aptitude
Nucleus Accumbens
Nicotinic Receptors
Cholinergic Antagonists
Smoking Cessation
Sucrose
Glutamic Acid
Dopamine

Keywords

  • Drug discrimination
  • Interoceptive stimulus
  • Iptakalim
  • Nicotine dependence
  • Pavlovian conditioning
  • Self-administration
  • Smoking
  • Tobacco

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine. / Charntikov, S.; Swalve, N.; Pittenger, S.; Fink, K.; Schepers, S.; Hadlock, G. C.; Fleckenstein, A. E.; Hu, G.; Li, Ming; Bevins, Rick A.

In: Neuropharmacology, Vol. 75, 01.01.2013, p. 138-144.

Research output: Contribution to journalArticle

Charntikov, S, Swalve, N, Pittenger, S, Fink, K, Schepers, S, Hadlock, GC, Fleckenstein, AE, Hu, G, Li, M & Bevins, RA 2013, 'Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine', Neuropharmacology, vol. 75, pp. 138-144. https://doi.org/10.1016/j.neuropharm.2013.07.019
Charntikov, S. ; Swalve, N. ; Pittenger, S. ; Fink, K. ; Schepers, S. ; Hadlock, G. C. ; Fleckenstein, A. E. ; Hu, G. ; Li, Ming ; Bevins, Rick A. / Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine. In: Neuropharmacology. 2013 ; Vol. 75. pp. 138-144.
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