Browsing by Author "Albrecht, Daniel S."

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    Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics
    (Elsevier, 2016-03) Yoder, Karmen K.; Albrecht, Daniel S.; Dzemidzic, Mario; Normandin, Marc D.; Federici, Lauren M.; Graves, Tammy; Herring, Christine M.; Hile, Karen L.; Walters, James W.; Liang, Tiebing; Plawecki, Martin H.; O'Connor, Sean; Kareken, David A.; Department of Radiology and Imaging Sciences, IU School of Medicine
    Background Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). Methods Twenty-four SD and twenty-one NTS received two [11C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then “clamped.” The alcohol clamp was started 5 min after scan start, with a linear increase in BrAC over 15 min to the target of 80 mg%, the legal threshold for intoxication. Target BrAC was maintained for 30 min. Voxel-wise binding potential (BPND) was estimated with MRTM2. Results IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. Conclusions Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD.
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    Differential dopamine function in fibromyalgia
    (Springer, 2016-09) Albrecht, Daniel S.; MacKie, Palmer J.; Kareken, David A.; Hutchins, Gary D.; Chumin, Evgeny J.; Christian, Bradley T.; Yoder, Karmen K.; Radiology and Imaging Sciences, School of Medicine
    Approximately 30% of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [18F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and eleven female controls completed study procedures. Subjects received one FAL PET scan while performing a “2-back” task, and one while performing a “0-back” (attentional control, “baseline”) task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.
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    Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers
    (Springer-Verlag, 2015-06) Oberlin, Brandon G.; Albrecht, Daniel S.; Herring, Christine M.; Walters, James W.; Hile, Karen L.; Kareken, David A.; Yoder, Karmen K.; Department of Radiology and Imaging Sciences, IU School of Medicine
    RATIONALE: Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood. OBJECTIVES: To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD). METHODS: NTS subjects (n = 10) and SD (n = 13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND. RESULTS: Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST. CONCLUSIONS: Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures.
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    Reliability of Striatal [11C]Raclopride Binding in Smokers Wearing Transdermal Nicotine Patches
    (Springer, 2012-02) Yoder, Karmen K.; Albrecht, Daniel S.; Kareken, David A.; Federici, Lauren M.; Perry, Kevin M.; Patton, Elizabeth A.; Zheng, Qi-Huang; Mock, Bruce H.; O’Connor, Sean J.; Herring, Christine M.; Department of Medicine, IU School of Medicine
    PURPOSE: In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches. METHODS: Eleven male smokers were scanned twice with RAC on separate days while wearing TNP. RESULTS: Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 (p < 0.0001). CONCLUSION: Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine.
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    URINE THC METABOLITE LEVELS CORRELATE WITH STRIATAL D2/D3 RECEPTOR AVAILABILITY
    (Office of the Vice Chancellor for Research, 2012-04-13) Albrecht, Daniel S.; Skosnik, Patrick D.; Vollmer, Jennifer M.; Brumbaugh, Margaret S.; Perry, Kevin M.; Zheng, Qi-Huang; Federici, Lauren A.; Patton, Elizabeth A.; Herring, Christine M.; Yoder, Karmen K.
    Rationale: Although the incidence of cannabis abuse/dependence in Americans is rising, the neurobiology of cannabis addiction is not well understood. Previous PET and SPECT studies have demonstrated deficits in striatal D2/D3 receptor availability in several substance-dependent populations. However, this has not been studied in chronic cannabis users. Objective: The purpose of this study was to compare striatal D2/D3 receptor availability between currently-using chronic cannabis users and healthy controls. Methods: Eighteen right-handed males, 18-34 years of age, were studied. Ten subjects were chronic cannabis users; eight were demographically matched controls. Subjects underwent a [11C]raclopride (RAC) PET scan. On the scan day, urine samples were obtained from cannabis users for quantification of urine Δ-9-tetrahydrocannabinol (THC; the active compound in cannabis smoke) and THC metabolites (11-nor-Δ-9-THC-9-carboxylic acid and 11-hydroxy-THC). Striatal RAC binding potential (BPND) was used as an index of D2/D3 receptor availability; this parameter was estimated at each image voxel for every subject. SPM5 software was used to test for differences in BPND between groups and, in cannabis subjects, for associations between BPND and markers of cannabis use. Results: There were no differences in D2/D3 receptor availability between cannabis users and controls. Smokers of either cannabis and/or tobacco had 10.2% lower BPND values than nonsmokers in the bilateral putamen (“any-smokers”: 2.66 ± 0.2; nonsmokers: 2.97 ± 0.2). In cannabis users, RAC BPND values were negatively associated with both urine levels of cannabis metabolites and self-report of recent cannabis consumption. Conclusions: There is an inverse relationship between chronic cannabis use and striatal RAC BPND. This may be caused by inhibition of monoamine oxidase (MAO) by the pyrolyzation of cannabis, which could lead to increased endogenous dopamine levels (and hence, lower BPND in heavier users). Additional studies are needed to identify the neurochemical consequences of chronic cannabis use on the dopamine system.