Behavior Genetics

, Volume 37, Issue 1, pp 119–145

Genetics of Dopamine and its Contribution to Cocaine Addiction

  • Colin N. Haile
  • Thomas R. Kosten
  • Therese A. Kosten
Original Paper

DOI: 10.1007/s10519-006-9115-2

Cite this article as:
Haile, C.N., Kosten, T.R. & Kosten, T.A. Behav Genet (2007) 37: 119. doi:10.1007/s10519-006-9115-2

Abstract

Cocaine addiction is a major health and social problem for which there are presently no effective pharmacotherapies. Many of the most promising medications target dopamine based on the large literature that supports its role in addiction. Recent studies show that genetic factors are also important. Rodent models and gene knock-out technology have helped elucidate the involvement of specific genes in the function of the dopamine reward system and intracellular cascades that lead to neuronal changes in this system. Human epidemiological, linkage, and association studies have identified allelic variants (polymorphisms) that give rise to altered metabolism of dopamine and its functional consequences. Individuals with these polymorphisms respond differently to psychostimulants and possibly to pharmacotherapies. Here we review the literature on genetic variations that affect dopamine neurotransmission, responses to psychostimulants and potential treatments for cocaine addiction. Behavioral responses to psychostimulants in animals with different or modified genetics in dopamine signaling are discussed. We also review polymorphisms in humans that affect dopaminergic neurotransmission and alter the subjective effects of psychostimulants. Pharmacotherapies may have increased efficacy when targeted to individuals possessing specific genetic polymophisms in dopamine’s metabolic and intracellular messenger systems.

Keywords

Polymorphism Drug response Microarray Disulfiram cAMP CREB Transduction Intracellular Addiction Genetic models Inbred rats Mesolimbic DBH Pharmacotherapies Epigenetics Gene expression 

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Colin N. Haile
    • 1
    • 2
  • Thomas R. Kosten
    • 1
    • 2
  • Therese A. Kosten
    • 1
    • 2
  1. 1.Michael E. DeBakey VA Medical CenterHoustonUSA
  2. 2.Meninger Department of PsychiatryBaylor College of MedicineHoustonUSA

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