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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
1P01DA031656-01A1
Application #
8311877
Study Section
Special Emphasis Panel (ZRG1-IFCN-H (40))
Project Start
Project End
Budget Start
2012-04-15
Budget End
2013-03-31
Support Year
1
Fiscal Year
2012
Total Cost
$274,450
Indirect Cost
$93,886
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Pitchers, Kyle K; Flagel, Shelly B; O'Donnell, Elizabeth G et al. (2015) Individual variation in the propensity to attribute incentive salience to a food cue: influence of sex. Behav Brain Res 278:462-9
Saunders, Benjamin T; O'Donnell, Elizabeth G; Aurbach, Elyse L et al. (2014) A cocaine context renews drug seeking preferentially in a subset of individuals. Neuropsychopharmacology 39:2816-23
Robinson, Terry E; Yager, Lindsay M; Cogan, Elizabeth S et al. (2014) On the motivational properties of reward cues: Individual differences. Neuropharmacology 76 Pt B:450-9
Sarter, Martin; Albin, Roger L; Kucinski, Aaron et al. (2014) Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function. Exp Neurol 257:120-9
Meyer, Paul J; Cogan, Elizabeth S; Robinson, Terry E (2014) The form of a conditioned stimulus can influence the degree to which it acquires incentive motivational properties. PLoS One 9:e98163
Vander Weele, Caitlin M; Porter-Stransky, Kirsten A; Mabrouk, Omar S et al. (2014) Rapid dopamine transmission within the nucleus accumbens: dramatic difference between morphine and oxycodone delivery. Eur J Neurosci 40:3041-54
Sarter, Martin; Lustig, Cindy; Howe, William M et al. (2014) Deterministic functions of cortical acetylcholine. Eur J Neurosci 39:1912-20
Lesaint, Florian; Sigaud, Olivier; Flagel, Shelly B et al. (2014) Modelling individual differences in the form of Pavlovian conditioned approach responses: a dual learning systems approach with factored representations. PLoS Comput Biol 10:e1003466
Parker, Clarissa C; Chen, Hao; Flagel, Shelly B et al. (2014) Rats are the smart choice: Rationale for a renewed focus on rats in behavioral genetics. Neuropharmacology 76 Pt B:250-8
Saunders, Benjamin T; Yager, Lindsay M; Robinson, Terry E (2013) Preclinical studies shed light on individual variation in addiction vulnerability. Neuropsychopharmacology 38:249-50

Showing the most recent 10 out of 16 publications