While the speed of delivery of drugs of abuse to the brain are thought to underlie their addictive potential, no research has focused on individual differences in speed of psychostimulant-induced high and liking and whether such differences are reflected at the level of the brain, personality, or genetics. Yet, preliminary data from our research group indicates there are dramatic differences in the temporal profile of subjective responses to oral d-amphetamine. The research proposed in this fellowship will use Positron Emission Tomography (PET) to assess multiple aspects of dopamine system function (striatal and extrastriatal D2-like binding potential, dopamine transporter levels, and d-amphetamine-induced dopamine release) and relate these PET measures to differences in positive subjective responses (drug high and liking) to d-amphetamine, with a particular emphasis on the timing of peak positive subjective drug effects. Furthermore, the proposed research will assess how individual differences in dopamine system function and the positive subjective effects of d-amphetamine vary with personality traits and genetic polymorphisms in healthy adults. Specifically, we will investigate the role of commonly studied polymorphisms in dopamine-related genes as well as a signal nucleotide polymorphism in the cadherin 13 gene previously found to be associated with the positive subjective effects of d-amphetamine in a genome wide association study. The goal of this research plan is to better understand individual differences that confer potential risk for psychostimulant addiction including a fast rise in dopamine and increased subjective high/liking after drug intake. The applicant's long-term goals are to identify how differences in dopamine system function relate to addiction risk at the level of behavioral endophenotypes including subjective drug high/liking time to peak, novelty seeking, and impulsivity (including steep temporal discounting). This fellowship will help the applicant develop expertise in measuring variation in the dopamine system (through PET and genetic approaches) and prepare him for a productive career as an independent investigator of dopamine's role in addiction risk, externalizing behaviors, and other traits often associated with drug addiction.

Public Health Relevance

Differences in the speed of delivery of drugs of abuse as well as the subjective high they produce are believed to relate to their addiction potential. This research fellowship will investigate whether observed differences in the timing of subjective psychostimulant effects are related to measurable differences in the functioning of the neurotransmitter dopamine, personality traits, and genetics. By understanding how these factors affect individual differences in drug responsivity we hope to identify potential biological and behavioral markers of psychostimulant addiction risk.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA041157-01
Application #
9050120
Study Section
Special Emphasis Panel (ZRG1-F02A-J (20)L)
Program Officer
Gordon, Harold
Project Start
2016-06-01
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
1
Fiscal Year
2016
Total Cost
$54,294
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37240
Smith, Christopher T; Dang, Linh C; Burgess, Leah L et al. (2018) Lack of consistent sex differences in D-amphetamine-induced dopamine release measured with [18F]fallypride PET. Psychopharmacology (Berl) :
Stark, Adam J; Smith, Christopher T; Lin, Ya-Chen et al. (2018) Nigrostriatal and Mesolimbic D2/3 Receptor Expression in Parkinson's Disease Patients with Compulsive Reward-Driven Behaviors. J Neurosci 38:3230-3239
Smith, Christopher T; San Juan, M Danica; Dang, Linh C et al. (2018) Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults. Transl Psychiatry 8:269
Stark, Adam J; Smith, Christopher T; Petersen, Kalen J et al. (2018) [18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease. Neuroimage Clin 18:433-442
Dang, Linh C; Samanez-Larkin, Gregory R; Smith, Christopher T et al. (2018) FTO affects food cravings and interacts with age to influence age-related decline in food cravings. Physiol Behav 192:188-193
Smith, Christopher T; Crawford, Jennifer L; Dang, Linh C et al. (2017) Partial-volume correction increases estimated dopamine D2-like receptor binding potential and reduces adult age differences. J Cereb Blood Flow Metab :271678X17737693
Smith, C T; Dang, L C; Buckholtz, J W et al. (2017) The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Transl Psychiatry 7:e1091
Smith, Christopher T; Dang, Linh C; Cowan, Ronald L et al. (2016) Variability in paralimbic dopamine signaling correlates with subjective responses to d-amphetamine. Neuropharmacology 108:394-402