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Séminaire impromptu - Diana MartinezDopamine and Addiction: using PET to explore the neurobiology of substance abuse

Abstract :

The involvement of dopamine in addiction has its origins in studies investigating reward and reinforced behavior in preclinical studies.
Much of this research has been explored in the human brain using Positron Emission Tomography (PET) imaging of striatal dopamine transmission. These studies show that addiction is associated with a decrease in dopamine D2/3 receptors and a decrease in pre-synaptic dopamine release, and that this decrease occurs across different types of addiction, including cocaine, alcohol, and heroin dependence.

However, these imaging studies also show that, in cocaine abuse, blunted dopamine transmission is predictive of cocaine seeking behavior. Low D2/3 receptor binding and low dopamine release are associated with the choice to self-administer cocaine over alternative reinforcers, which can be viewed as a failure to shift between competing rewards. It is striking that addiction to different substances of abuse are accompanied by the same alteration in neurobiology, independent of their primary impact on the dopaminergic system.
Moreover, similar alterations of the dopaminergic transmission and D2-like receptor system have been described in psychiatric diseases other than addiction. Although these psychiatric disorders differ in their phenomenology, they share a common deficit in reward-related behavior, particularly with respect to impulsivity and motivation.
This presentation will describe the animal and human studies that link alterations in dopamine transmission and the D2 receptors with impulsive and motivated behavior. The hypothesis that these alterations in dopamine transmission represent the neurobiological underpinnings that facilitate impulsivity and undermine motivation, rather than the only the consequences of addiction itself, will be discussed.

Selected publications

  1. Martinez D, Broft A, Foltin RW, Slifstein M, Hwang DR, Huang Y, Perez A, Frankle WG, Cooper T, Kleber HD, Fischman MW, Laruelle M.  Cocaine dependence and D2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior.  Neuropsychopharmacology. 2004 Jun;29(6):1190-202.
  2. Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A. . Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum.  Biological Psychiatry. 2005 Nov 15; 58(10):779-86.
  1. Martinez D, Narendran R, Foltin RW, Slifstein M, Hwang DR, Broft A, Huang Y, Cooper TB, Fischman MW, Kleber HD, Laruelle M. Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry. 2007 Apr;164(4):622-9.
  2. Martinez D, Greene K, Broft A, Kumar D, Liu F, Narendran R, Slifstein M, Van Heertum R, Kleber HD. Lower Level of Endogenous Dopamine in Patients With Cocaine Dependence: Findings From PET Imaging of D2/D3 Receptors Following Acute Dopamine Depletion. Am J Psychiatry. 2009 Oct;166(10):1170-7.
  3. Martinez D, Carpenter KM, Liu F, Slifstein M, Broft A, Friedman AC, Kumar D, Van Heertum R, Kleber HD, Nunes E. Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment. Am J Psychiatry. 2011 Jun;168(6):634-41.
  4. Trifilieff P, Martinez D. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology. 2013 Jul 10
  1. Martinez D, Saccone PA, Liu F, Slifstein M, Orlowska D, Grassetti A, Cook S, Broft A, Van Heertum R, Comer SD. Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction. Biol Psychiatry. 2012 Feb 1;71(3):192-8.
  1. Trifilieff P, Feng B, Urizar E, Winiger V, Ward RD, Taylor KM, Martinez D, Moore H, Balsam PD, Simpson EH, Javitch JA. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry. 2013 Sep;18(9):1025-33.

Scientific focus :

Associate Professor
Columbia University/New York State Psychiatric Institute
Department of Psychiatry
1051 Riverside Drive
New York, NY 10032
United States of America