Chronic smoking is a national public health problem. Associative-based interventions (cue-exposure therapy) can be effective at reducing smoking and decreasing relapse rates, indicating that acquired associations with nicotine contribute to chronic smoking and relapse. The long-term goal of this research program is to elucidate these associative processes and their role in chronic nicotine use. Pavlovian conditioned associations between a conditioned stimulus (CS) and an unconditioned stimulus (US) is one such process. In contrast to research treating nicotine as a US, little work has explored the possibility that the pharmacological effects of nicotine might serve as a CS and acquire additional excitatory properties. The present application will eliminate this deficit using a rat model. In this model, nicotine (CS) is reliably paired with the appetitive effects of sucrose (US). An association is evidenced when nicotine differentially evokes anticipatory food-seeking behavior.
Specific Aim 1 will test whether changing the nature of the nicotine CS alters development or expression of conditioned responding; alterations include changes in nicotine dose and time between nicotine administration and testing.
Aim 2 will test whether an associative learning or a state-dependent learning process is responsible for differential control of food seeking by nicotine.
Aim 3 will assess the ability of several ligands (ABT-418, bupropion, nornicotine, cytisine, epibatidine) to prompt nicotine-like conditioned responding (stimulus substitution). Differential substitution patterns will provide insight into the neurobiological processes mediating the CS effects of nicotine.
Aim 4 will assess whether extinction with a ligand that shares stimulus properties with nicotine will lead to the development of a competing association that transfers to a nicotine CS. This transfer of extinction (associative substitution) would be evidenced if rats trained with a nicotine CS, but receive extinction with another drug, show loss of conditioned responding when retested with the unextinguished nicotine CS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA018114-05
Application #
7459022
Study Section
Special Emphasis Panel (ZRG1-BBBP-H (02))
Program Officer
Schnur, Paul
Project Start
2004-08-01
Project End
2009-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$167,646
Indirect Cost
Name
University of Nebraska Lincoln
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
555456995
City
Lincoln
State
NE
Country
United States
Zip Code
68588
Charntikov, S; Falco, A M; Fink, K et al. (2017) The effect of sazetidine-A and other nicotinic ligands on nicotine controlled goal-tracking in female and male rats. Neuropharmacology 113:354-366
Charntikov, Sergios; deWit, Nicole R; Bevins, Rick A (2014) Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion. Neuropharmacology 86:181-91
Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A (2013) Interoceptive conditioning with the nicotine stimulus: extinction learning as a method for assessing stimulus similarity across doses. Behav Pharmacol 24:45-54
Pittenger, Steven T; Bevins, Rick A (2013) Interoceptive conditioning in rats: effects of using a single training dose or a set of 5 different doses of nicotine. Pharmacol Biochem Behav 114-115:82-9
Pittenger, Steven T; Bevins, Rick A (2013) Interoceptive conditioning with a nicotine stimulus is susceptible to reinforcer devaluation. Behav Neurosci 127:465-73
Charntikov, S; Swalve, N; Pittenger, S et al. (2013) Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine. Neuropharmacology 75:138-44
Barret, Scott T; Bevins, Rick A (2013) Nicotine enhances operant responding for qualitatively distinct reinforcers under maintenance and extinction conditions. Pharmacol Biochem Behav 114-115:9-15
Barrett, Scott T; Bevins, Rick A (2012) A quantitative analysis of the reward-enhancing effects of nicotine using reinforcer demand. Behav Pharmacol 23:781-9
Charntikov, Sergios; Tracy, Matthew E; Zhao, Changjiu et al. (2012) Conditioned response evoked by nicotine conditioned stimulus preferentially induces c-Fos expression in medial regions of caudate-putamen. Neuropsychopharmacology 37:876-84
Bevins, Rick A; Barrett, Scott T; Polewan, Robert J et al. (2012) Disentangling the nature of the nicotine stimulus. Behav Processes 90:28-33

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