Previous clinical and pre-clinical studies have shown that the dysregulation in dopamine transmission plays a critical role in substance abuse. The studies presented in this application include the candidate's work characterizing the alteration in dopamine transmission seen in addiction. These studies include research done in cocaine, alcohol, and heroin dependence, and show that each of these disorders is associated with a loss of D2/3 receptor binding and pre-synaptic dopamine transmission. Importantly, the work done in cocaine dependence shows that dopamine transmission is predictive of relapse. The next step is to explore the mechanisms that contribute to dopamine dysregulation in addition to studying other neurotransmitter systems that directly regulate dopamine transmission. These studies include imaging micriglial activation, in addition to the kappa and neurotensin receptors systems. The candidate developed her PET imaging career through the K23 award mechanism. Due to the support provided by that award, she was able to pursue a career in imaging studies in substance dependent populations. As an independent researcher, the candidate has continued this line of work. In addition, the candidate has pursued numerous collaborations in an effort to bring PET radioligand imaging into more types of clinical research. This application for a K02 award will allow the candidate's career to continue uninterrupted as she pursues new directions in PET imaging.
Previous work performed by the applicant for this award have shown that dopamine is involved in drug addiction. The next set of studies will examine the cause of the changes in brain dopamine and ways to correct this deficit.
|Salling, Michael C; Martinez, Diana (2016) Brain Stimulation in Addiction. Neuropsychopharmacology 41:2798-2809|
|Cooper, Ziva D; Johnson, Kirk W; Pavlicova, Martina et al. (2016) The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers. Addict Biol 21:895-903|
|Chavkin, Charles; Martinez, Diana (2015) Kappa Antagonist JDTic in Phase 1 Clinical Trial. Neuropsychopharmacology 40:2057-8|
|Broft, Allegra; Slifstein, Mark; Osborne, Joseph et al. (2015) Striatal dopamine type 2 receptor availability in anorexia nervosa. Psychiatry Res 233:380-7|
|Horga, Guillermo; Maia, Tiago V; Marsh, Rachel et al. (2015) Changes in corticostriatal connectivity during reinforcement learning in humans. Hum Brain Mapp 36:793-803|
|Trifilieff, Pierre; Martinez, Diana (2014) Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology 76 Pt B:498-509|
|Martinez, Diana; Slifstein, Mark; Nabulsi, Nabeel et al. (2014) Imaging glutamate homeostasis in cocaine addiction with the metabotropic glutamate receptor 5 positron emission tomography radiotracer [(11)C]ABP688 and magnetic resonance spectroscopy. Biol Psychiatry 75:165-71|
|Luo, Sean X; Martinez, Diana; Carpenter, Kenneth M et al. (2014) Multimodal predictive modeling of individual treatment outcome in cocaine dependence with combined neuroimaging and behavioral predictors. Drug Alcohol Depend 143:29-35|
|Trifilieff, Pierre; Martinez, Diana (2014) Blunted dopamine release as a biomarker for vulnerability for substance use disorders. Biol Psychiatry 76:4-5|
|Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun et al. (2014) Neural correlates of reward-based spatial learning in persons with cocaine dependence. Neuropsychopharmacology 39:545-55|
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