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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Oregon Health and Science University
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Shabani, Shkelzen; Schmidt, Bryan; Ghimire, Bikalpa et al. (2018) Depression-like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake. Genes Brain Behav :e12533
Eshleman, Amy J; Nagarajan, Shanthi; Wolfrum, Katherine M et al. (2018) Structure-activity relationships of bath salt components: substituted cathinones and benzofurans at biogenic amine transporters. Psychopharmacology (Berl) :
McCready, Holly; Kohno, Milky; Kolessar, Michael et al. (2018) Functional MRI and delay discounting in patients infected with hepatitis C. J Neurovirol 24:738-751
Loftis, Jennifer M; Valerio, Juno; Taylor, Jonathan et al. (2018) S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood-Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder. Alcohol Clin Exp Res :
Eshleman, Amy J; Wolfrum, Katherine M; Reed, John F et al. (2018) Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors. Biochem Pharmacol 158:27-34
Tosh, Dilip K; Ciancetta, Antonella; Mannes, Philip et al. (2018) Repurposing of a Nucleoside Scaffold from Adenosine Receptor Agonists to Opioid Receptor Antagonists. ACS Omega 3:12658-12678
McCarty, Dennis; Priest, Kelsey C; Korthuis, P Todd (2018) Treatment and Prevention of Opioid Use Disorder: Challenges and Opportunities. Annu Rev Public Health 39:525-541
Eastwood, Emily C; Eshleman, Amy J; Janowsky, Aaron et al. (2018) Verification of a genetic locus for methamphetamine intake and the impact of morphine. Mamm Genome 29:260-272
Kohno, Milky; Dennis, Laura E; McCready, Holly et al. (2018) A preliminary randomized clinical trial of naltrexone reduces striatal resting state functional connectivity in people with methamphetamine use disorder. Drug Alcohol Depend 192:186-192
Holton, Dwight; White, Elizabeth; McCarty, Dennis (2018) Public Health Policy Strategies to Address the Opioid Epidemic. Clin Pharmacol Ther 103:959-962

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