Cues associated with food and drug rewards acquire 1) predictive properties, and the ability to evoke conditioned responses, and 2) incentive properties, and thus the ability to attract, reinforce, and motivate behavior. These latter properties may be especially important in the development of compulsive behavioral disorders, including addiction. However, predictive cues do not necessarily have the ability to act as incentive stimuli. In fact, there are substantial individual differences in the ability of cues to influence behavior. For example, while some people are able to use drugs casually throughout their lifetime, others become addicted, having difficulty remaining abstinent, especially in the presence of people, places, and other cues associated with drug-taking. By examining the behavioral responses to food cues, we have identified rats that attribute incentive value to these cues (""""""""sign-trackers""""""""), and are more sensitive to the effects of drug cues on drug-taking behavior and relapse. In contrast, """"""""goal-trackers"""""""" do not attribute incentive value to food cues and are unaffected by drug cues. Studies of cue-evoked changes in brain activity have found that ventral regions of the basal ganglia (including the nucleus accumbens [NAcc] and ventral pallidum [VP]) process information related to both food and drug cues. However, until recently, it has been difficult to delineate what aspects (i.e., predictive or incentive) of these cues are processed, and whether the processsing of incentive value is altered by abused drugs. The experiments described within this proposal will utilize individual differences of sign- and goal-trackers to determine whether the NAcc and VP process incentive vs. predictive properties of food cues in sign- and goal-trackers, and to what extent the neurochemical dopamine is involved. To this end, we will measure the neural response to cues in Pavlovian and drug self-administration experiments using in-vivo single-unit recordings. Our overall hypothesis is that VP and NAcc neurons will be more responsive to the incentive properties than to the predictive properties of reward cues when presented within these experiments.

Public Health Relevance

Some people use drugs casually;others become addicted and have difficulty remaining abstinent in the presence of cues associated with drug-taking. We will compare the brain's responses to various cues in rats that are either susceptible or resistant to the effects of these cues. These experiments will help explain the sensitivity to food- and drug-related cues and lead to interventions to reduce their impact on drug-taking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA031656-03
Application #
8638915
Study Section
Special Emphasis Panel (ZRG1-IFCN-H)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
3
Fiscal Year
2014
Total Cost
$271,181
Indirect Cost
$96,788
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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
Pitchers, Kyle K; Wood, Taylor R; Skrzynski, Cari J et al. (2017) The ability for cocaine and cocaine-associated cues to compete for attention. Behav Brain Res 320:302-315
Flagel, Shelly B; Robinson, Terry E (2017) Neurobiological Basis of Individual Variation in Stimulus-Reward Learning. Curr Opin Behav Sci 13:178-185
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
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
Koshy Cherian, Ajeesh; Kucinski, Aaron; Pitchers, Kyle et al. (2017) Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases. J Neurosci 37:2947-2959
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
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
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
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 :

Showing the most recent 10 out of 41 publications