Addicts have great difficulty resisting stimuli (cues) that have been associated with drug use. Such cues unduly attract their attention, draw them to locations where drugs are located and motivate continued drug seeking behavior - often leading to relapse even in the face of an expressed desire to discontinue drug use. Drug cues are thought to acquire incentive motivational properties ("incentive salience") as a consequence of Pavlovian conditioning, whereby previously neutral stimuli acquire conditional stimulus (CS) properties. However, in preclinical studies using rats we have discovered that individuals vary markedly in the extent to which they attribute incentive salience to reward cues. A reward cue may act as a perfectly effective CS, evoking a conditional response (CR) in all animals, but function as a potent incentive stimulus only in some. Only if reward cues act as incentive stimuli do they come to attract, incite, provoke, spur and motivate, leading to potentially maladaptive behavior. We hypothesize, therefore, that individuals prone to attribute incentive salience to reward cues will have particular difficulty resisting them and will be especially vulnerable to develop addiction-like behavior. We propose a series of preclinical studies using rats to test this hypothesis, and to determine the relationship between this "trait", and others thought to confer vulnerability to addiction, including a propensity to make "impulsive actions'. Specific studies address the following key questions: (1) Is it possible to predict, prior to any drug experience, which individuals will attribute incentive salience to a drug cue? (2) Does variation in the propensity to attribute incentive salience to reward cues predict which individuals are susceptible to develop addiction-like behavior when they are given extended opportunity to self-administer drugs? (3) Does past experience with drugs increase the degree to which incentive value is attributed to drug cues? (4) Do the brain regions necessary for Pavlovian stimulus-reward learning differ in animals that do or do not attribute incentive salience to reward cues? These studies have the potential to fundamentally shift how we think about individual vulnerability to addiction, and point the way for better-targeted interventions.
Addiction is a major public health problem in the United States. The goal of this Project is to use a preclinical model to delineate the psychological and neurobiological basis of individual differences in vulnerability to develop addiction-like behavior, as this will help identify risk factors that will aid in the development of targeting interventions and treatments.
|Sarter, Martin; Lustig, Cindy; Blakely, Randy D et al. (2016) Cholinergic genetics of visual attention: Human and mouse choline transporter capacity variants influence distractibility. J Physiol Paris 110:10-18|
|Ahrens, Allison M; Singer, Bryan F; Fitzpatrick, Christopher J et al. (2016) Rats that sign-track are resistant to Pavlovian but not instrumental extinction. Behav Brain Res 296:418-30|
|Singer, Bryan F; Guptaroy, Bipasha; Austin, Curtis J et al. (2016) Individual variation in incentive salience attribution and accumbens dopamine transporter expression and function. Eur J Neurosci 43:662-70|
|Fitzpatrick, Christopher J; Perrine, Shane A; Ghoddoussi, Farhad et al. (2016) Sign-trackers have elevated myo-inositol in the nucleus accumbens and ventral hippocampus following Pavlovian conditioned approach. J Neurochem :|
|Gritton, Howard J; Howe, William M; Mallory, Caitlin S et al. (2016) Cortical cholinergic signaling controls the detection of cues. Proc Natl Acad Sci U S A 113:E1089-97|
|Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A et al. (2016) Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards. Eur J Neurosci 44:2431-2445|
|Sarter, Martin; Lustig, Cindy; Berry, Anne S et al. (2016) What do phasic cholinergic signals do? Neurobiol Learn Mem 130:135-41|
|Kawa, Alex B; Bentzley, Brandon S; Robinson, Terry E (2016) Less is more: prolonged intermittent access cocaine self-administration produces incentive-sensitization and addiction-like behavior. Psychopharmacology (Berl) 233:3587-602|
|Ahrens, Allison M; Meyer, Paul J; Ferguson, Lindsay M et al. (2016) Neural Activity in the Ventral Pallidum Encodes Variation in the Incentive Value of a Reward Cue. J Neurosci 36:7957-70|
|Fraser, Kurt M; Haight, Joshua L; Gardner, Eliot L et al. (2016) Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors. Behav Brain Res 305:87-99|
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