Theoretical and empirical approaches to drug abuse that include associative learning processes have lead to important advances in our understanding and treatment of drug dependence. These approaches typically treat the drug as an unconditioned stimulus (US). That is, the biological effects of the drug (e.g., reward, psychomotor stimulation) enter into an association with stimuli that reliably co-occur with these effects (e.g., paraphernalia, situational cues). Recent research has shown that the pharmacological (interoceptive) effects of a drug also serve as a CS for other rewarding USs. Such an appetitive conditioning history with a drug state could speed the trajectory from experimentation to dependence or increase the tenacity of the addiction. The experiments proposed in this application will test an important prediction of this perspective using a preclinical animal model in which nicotine functions as the CS. This research builds programmatically on our past research with nicotine. More specifically, rats will receive intravenous (IV) nicotine paired with brief access to a sucrose solution (i.e., an appetitive US). In preliminary research, the nicotine CS comes to evoke an appetitive CR (anticipatory sucrose-seeking behavior). Our working hypothesis attributes this CR to the interoceptive nicotine CS acquiring additional appetitive properties by virtue of being reliably paired with an appetitive outcome. This hypothesis is consistent with most Pavlovian conditioning theories and suggests that nicotine's ability to serve as a reward may be modified by an appetitive conditioning history. Accordingly, the main goal of this application is to programmatically test this prediction with a widely used preclinical model of drug reward-place conditioning. The following Aims will be used to accomplish this goal.
Specific Aim 1 will determine how conditioned responding varies as a function of IV nicotine dose (e.g., 0.005 to 0.06 mg/kg) used as the CS. In doing so, we will identify nicotine doses that have interoceptive stimulus properties that also acquired additional appetitive properties from this learning history.
Aim 2 will determine whether having this appetitive conditioning history will alter nicotine's ability to then function as a reward (i.e., US) in an IV nicotine place conditioning task. We expect an appetitive learning history with nicotine to potentiate its later rewarding effects.

Public Health Relevance

Tobacco use reflects a major health problem that results from an addiction to nicotine. With an estimated annual economic cost around $167 billion, this nicotine addiction is associated with a significant increase in heart disease and many forms of cancer;the health of non-tobacco users is also negatively affected by second-hand smoke. The potential benefits that would come from a better understanding of the etiology of tobacco dependence are enormous and is the reason the long-term goal of our research program is to elucidate potential associative learning processes contributing to nicotine dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA023951-02
Application #
7640668
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (02))
Program Officer
Schnur, Paul
Project Start
2008-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$169,682
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
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
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
Dion, Amanda M; Sanderson, Scott C; Murrin, L Charles et al. (2012) Diminished conditioned responding to the nicotine stimulus by antidepressant drugs with differing specificity for the serotonin and norepinephrine transporter. Pharmacol Biochem Behav 100:419-24
Murray, Jennifer E; Bevins, Rick A (2010) Cannabinoid conditioned reward and aversion: behavioral and neural processes. ACS Chem Neurosci 1:265-278
Wooters, Thomas E; Bevins, Rick A; Bardo, Michael T (2009) Neuropharmacology of the interoceptive stimulus properties of nicotine. Curr Drug Abuse Rev 2:243-55