One of the primary challenges with the treatment of dmg addiction is that most drug addicts are not able to refrain from taking drugs even though they desperately wish to quit, frequently relapsing even after long periods of abstinence. One powerful trigger for relapse is the presentation of environmental stimuli that were previously associated with drug taking (i.e., a drug-associated cues). Most importantly for this proposal, there is significant individual variation in the degree to which presentation of a drug-associated cue increases the incentive motivation to take drugs. Moreover, the degree that such cues increase the desire to take drug is correlated with how much the cue increases dopamine (DA) transmission, both in PET studies in humans and in preclinical studies in rats. Therefore, rodent studies can be used to study the relationship between the incentive value of drug-cues and DA signaling. In the current application, we propose to measure subsecond changes in DA concentration in freely moving rats and examine the relationship between phasic DA transmission and individual variation in the propensity to attribute incentive value to reward-predictive cues, especially drug-cues. This technology, fast-scan cyclic voltammetry (FSCV), can distinguish between specific aspects of DA transmission (such as release and uptake) and has been used to reveal novel neural consequences of cocaine intake and regional specificity associated with cue-cocaine conditioning. Here, we will use FSCV to determine if there are inherent differences in DA signaling pathways that predict individual variation in the propensity to attribute incentive value to reward-cues. We will then determine how incentive motivation impacts increased DA transmission by reward-predictive cues (including drug-associated cues) and how this is related to individual differences in drug-seeking and relapse. Given the enormous variation in the susceptibility to develop addiction, understanding the neurobiological basis of this susceptibility is critical for treatment of the disease.

Public Health Relevance

Addiction is a major public health problem in the United States. Very little is known about the neurobiology of individual differences associated with drug-seeking behavior. The goal of this Project is to to use a preclinical model to study neural encoding associted with individual differences in dmg-seeking. These experiments will facilitate the development of interventions and treatments of dmg addiction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1-IFCN-H)
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University of Michigan Ann Arbor
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Ahrens, Allison M; Ferguson, Lindsay M; Robinson, Terry E et al. (2018) Dynamic Encoding of Incentive Salience in the Ventral Pallidum: Dependence on the Form of the Reward Cue. eNeuro 5:
Sarter, Martin; Phillips, Kyra B (2018) The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models. Behav Neurosci 132:1-12
Kawa, Alex B; Robinson, Terry E (2018) Sex differences in incentive-sensitization produced by intermittent access cocaine self-administration. Psychopharmacology (Berl) :
Singer, Bryan F; Fadanelli, Monica; Kawa, Alex B et al. (2018) Are Cocaine-Seeking ""Habits"" Necessary for the Development of Addiction-Like Behavior in Rats? J Neurosci 38:60-73
Mabrouk, Omar S; Han, John L; Wong, Jenny-Marie T et al. (2018) The in Vivo Neurochemical Profile of Selectively Bred High-Responder and Low-Responder Rats Reveals Baseline, Cocaine-Evoked, and Novelty-Evoked Differences in Monoaminergic Systems. ACS Chem Neurosci 9:715-724
Cogan, Elizabeth S; Shapses, Mark A; Robinson, Terry E et al. (2018) Disrupting reconsolidation: memory erasure or blunting of emotional/motivational value? Neuropsychopharmacology :
Pitchers, Kyle K; Kane, Louisa F; Kim, Youngsoo et al. (2017) 'Hot' vs. 'cold' behavioural-cognitive styles: motivational-dopaminergic vs. cognitive-cholinergic processing of a Pavlovian cocaine cue in sign- and goal-tracking rats. Eur J Neurosci 46:2768-2781
Singer, Bryan F; Bryan, Myranda A; Popov, Pavlo et al. (2017) Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine. Behav Brain Res 324:66-70
Pitchers, Kyle K; Phillips, Kyra B; Jones, Jonte L et al. (2017) Diverse Roads to Relapse: A Discriminative Cue Signaling Cocaine Availability Is More Effective in Renewing Cocaine Seeking in Goal Trackers Than Sign Trackers and Depends on Basal Forebrain Cholinergic Activity. J Neurosci 37:7198-7208
Turner, Cortney A; Flagel, Shelly B; Blandino Jr, Peter et al. (2017) Utilizing a unique animal model to better understand human temperament. Curr Opin Behav Sci 14:108-114

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