Specific Aim 1: Quantify and characterize the parametric variation of cerebral response to delay, probability, and reward magnitude during decision making in MA dependent individuals vs Controls.
Specific Aim 2 : Quantify disruptions in cerebral connectivity as a factor underlying increased impulsivity in MA using functional correlation, diffusion-tensor imaging (DTI) and voxel based morphometry (VBM).
Specific Aim 3 : Investigate, in humans and rodents, the hypothesis that neuroimmune disruption of network connectivity contributes to impulsive choice in methamphetamine dependence METHODS: Forty-five actively using methamphetamine (MA) dependent individuals, 45 MA dependent patients in early (1 to 6 months) remission and 45 controls will be recruited from local residential treatment programs and by advertisement. Subjects will be evaluated with functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and voxel based morphometry (VBM) in order to identify the anatomical and functional networks that underlie impulsive choice. Component 9 will expose mice from two lines selected for high and low MA drinking (Component 9), to chronic MA administration, chronic administration followed by abstinence and saline vehicle (total of 120 mice) and then train them to perform an animal version of the delay discounting task. Component 9 will provide brains of these mice to this component for ex-vivo MRI scanning. We will perform parallel analyses in mouse and human brains. Measures of immune dysregulation and differential gene expression (from Component 8) will be investigated as factors responsible for disruption of decision networks in humans and in animals performing impulsivity tasks.
MA dependence has neuropsychiatric, economic and legal costs to individuals and communities. In particular, impulsivity in MA user may contribute both to the high legal cost associated with MA dependence and to the difficulty patients have maintaining abstinence. This project addresses critical aspects of impulsive choice in MA dependent individuals and has important implications for novel cognitive and pharmacological interventions.
|Szumlinski, Karen K; Lominac, Kevin D; Campbell, Rianne R et al. (2016) Methamphetamine Addiction Vulnerability: The Glutamate, the Bad, and the Ugly. Biol Psychiatry :|
|Li, Minghua; Underhill, Suzanne M; Reed, Cheryl et al. (2016) Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons. Neuropsychopharmacology :|
|Lominac, Kevin D; Quadir, Sema G; Barrett, Hannah M et al. (2016) Prefrontal glutamate correlates of methamphetamine sensitization and preference. Eur J Neurosci 43:689-702|
|Loftis, Jennifer M; Lim, Miranda M (2016) Sleep disturbance in substance use disorders and comorbid chronic viral infections. Addiction 111:1093-4|
|Ellis, Carilyn; Hoffman, William; Jaehnert, Sarah et al. (2016) Everyday problems with executive dysfunction and impulsivity in adults recovering from methamphetamine addiction. Addict Disord Their Treat 15:1-5|
|Kim, Hyunjee; Hartung, Daniel M; Jacob, Reside L et al. (2016) The Concentration of Opioid Prescriptions by Providers and Among Patients in the Oregon Medicaid Program. Psychiatr Serv 67:397-404|
|Janowsky, Aaron; Tosh, Dilip K; Eshleman, Amy J et al. (2016) Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine. J Pharmacol Exp Ther 357:24-35|
|Greenberg, G D; Huang, L C; Spence, S E et al. (2016) Nest building is a novel method for indexing severity of alcohol withdrawal in mice. Behav Brain Res 302:182-90|
|Zou, Mu-Fa; Keck, Thomas M; Kumar, Vivek et al. (2016) Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity. J Med Chem 59:2973-88|
|Abraham, Antony D; Neve, Kim A; Lattal, K Matthew (2016) Effects of D1 receptor knockout on fear and reward learning. Neurobiol Learn Mem 133:265-73|
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