High dose exposure of animals to methamphetamine [MA] causes significant damage to frontostriatal brain regions, which are relatively rich in dopaminergic [DA] and serotonergic [5-HT] innervation. Although animal models of drug addiction are extremely valuable, convergent findings from human studies are critical if one is to understand the impact of long-term MA use on the human brain. The goal of this proposal is to examine the effects of long-term effects of MA use in frontostriatal regions using proton magnetic resonance spectroscopy [MRS] in conjunction with mature neurons (primarily N- acetyl aspartase [NAA], high energy metabolic products (phosphocreatine and creatine [Cr], cell membrane synthesis or degradation (choline [Cho]), and glia (myoInositol [mI). MRS is a safe non-invasive tool that can detect certain proton spectroscopic metabolite patterns associated with brain damage and has been validated as a viable tool in detecting neuronal damage in both animals and humans. The interdisciplinary approach of MRS and cognitive assessment will yield valuable data essential for understanding the cognitive sequelae of neuronal damage resulting from MA abuse. Our preliminary data from methamphetamine dependent (MD) subjects (n=9) reveal likely neuronal damage in the prefrontal cortex [PFC] and anterior cingulate [ACC] as well as deficits on attentional tasks subserved by these regions. The proposed work is essential to confirm these clinically important findings by testing a larger sample of MD subjects and controls, using MRS in conjunction with sensitive computerized tasks of attention and memory. NAA, Choline, myo- Inositol and creatine will be measured in the PFC (dorsal and ventral), ACC, striatum, and control structures (primary visual cortex). Group differences in levels of NAA, Chol, mI, and Cr in the above regions will be determined by repeated measured analysis of variance. A similar analysis approach will be applied to the behavioral data. Correlational analyses between cognitive measures and imaging data from specific hypothesized regions of interest will be conducted.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA014359-03
Application #
6717712
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Grant, Steven J
Project Start
2002-06-01
Project End
2007-02-28
Budget Start
2004-03-01
Budget End
2007-02-28
Support Year
3
Fiscal Year
2004
Total Cost
$222,750
Indirect Cost
Name
University of California Davis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Salo, Ruth; Buonocore, Michael H; Leamon, Martin et al. (2011) Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: a proton MRS study. Drug Alcohol Depend 113:133-8
Salo, R; Nordahl, T E; Buonocore, M H et al. (2011) Spatial inhibition and the visual cortex: a magnetic resonance spectroscopy imaging study. Neuropsychologia 49:830-838
Salo, Ruth; Flower, Keith; Kielstein, Anousheh et al. (2011) Psychiatric comorbidity in methamphetamine dependence. Psychiatry Res 186:356-61
Leamon, Martin H; Flower, Keith; Salo, Ruth E et al. (2010) Methamphetamine and paranoia: the methamphetamine experience questionnaire. Am J Addict 19:155-68
Salo, Ruth; Nordahl, Thomas E; Galloway, Gantt P et al. (2009) Drug abstinence and cognitive control in methamphetamine-dependent individuals. J Subst Abuse Treat 37:292-7
Salo, Ruth; Nordahl, Thomas E; Buonocore, Michael H et al. (2009) Cognitive control and white matter callosal microstructure in methamphetamine-dependent subjects: a diffusion tensor imaging study. Biol Psychiatry 65:122-8