V Adams

Washoe County Medical Examiner's Office, Reno, Nevada, United States

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Publications (6)47.33 Total impact

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    ABSTRACT: Phospholipids are essential components of cell membranes which may also function to mediate some of the behavioural effects of dopamine receptor stimulation caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest that abnormal brain metabolism of phospholipids might explain some of the consequences of chronic exposure to drugs of abuse including drug craving. We previously reported decreased activity of calcium-stimulated phospholipase A(2) (Ca-PLA(2)) in autopsied putamen of human cocaine users. To establish the specificity of this change in phospholipid metabolism and whether decreased Ca-PLA(2) might be a general feature of all abused drugs which enhance dopaminergic neurotransmission, we measured activity of 11 major phospholipid metabolic enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of cocaine and of methamphetamine. Enzyme changes were restricted to the putamen which showed decreased (-21%, as compared with the control subjects) Ca-PLA(2) activity in users of methamphetamine and reduced (-31%) activity of phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic exposure to psychostimulant drugs might cause a compensatory downregulation of Ca-PLA(2) in dopamine-rich brain areas due to excessive dopamine-related stimulation of the enzyme. Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine.
    Drug and Alcohol Dependence 07/2002; 67(1):73-9. · 3.14 Impact Factor
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    ABSTRACT: To establish whether chronic opiate exposure might impair brain dopaminergic or serotonergic function in humans, we assessed biochemical indices of monoaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of the vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. In nucleus accumbens, levels of tyrosine hydroxylase protein (-25%) and those of the dopamine metabolite homovanillic acid (-33%) were reduced significantly together with a trend for decreased dopamine (-32%) concentration. These changes could reflect either a compensatory downregulation of dopamine biosynthesis in response to prolonged dopaminergic stimulation caused by heroin, or reduced axoplasmic transport of tyrosine hydroxylase. Striatal levels of serotonin were either normal or elevated whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were decreased by 27-38%. Our data suggest that chronic heroin exposure might produce a modest reduction in dopaminergic and serotonergic activity that could affect motivational state and impulse control, respectively.
    Neuropsychopharmacology 06/2001; 24(5):561-7. · 8.68 Impact Factor
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    ABSTRACT: Animal data have long suggested that an adaptive upregulation of nucleus accumbens dopamine D1 receptor function might underlie part of the dependency on drugs of abuse. We measured by quantitative immunoblotting protein levels of dopamine D1 and, for comparison, D2 receptors in brain of chronic users of methamphetamine, cocaine, and heroin. As compared with the controls, brain dopamine D1 receptor concentrations were selectively increased (by 44%) in the nucleus accumbens of the methamphetamine users, whereas a trend was observed in this brain area for reduced protein levels of the dopamine D2 receptor in all three drug groups (-25 to -37%; P < 0.05 for heroin group only). Our data support the hypothesis that aspects of the drug-dependent state in human methamphetamine users might be related to increased dopamine D1 receptor function in limbic brain.
    Molecular Psychiatry 11/2000; 5(6):664-72. · 15.15 Impact Factor
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    ABSTRACT: We measured concentrations of cocaine and its major metabolites (benzoylecgonine, ecgonine methylester, norcocaine, and cocaethylene) in 15 autopsied brain regions of 14 human chronic cocaine users. Only slight differences were observed in concentrations of cocaine and its metabolites amongst the examined brain areas. Although it is likely that some postmortem redistribution of the drug must have occurred, our data are consistent with the possibility that behaviorally relevant doses of cocaine are widely distributed throughout the brain of humans who use the drug on a chronic basis. Consideration should therefore be given to the possible pharmacological and toxicological actions of cocaine in both striatal and extra-striatal brain areas in human users of the drug.
    Journal of Forensic Sciences 10/2000; 45(5):1041-8. · 1.24 Impact Factor
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    ABSTRACT: Although the nucleus accumbens is assumed to be a critical brain "pleasure center," its function in humans is unknown. As animal data suggest that a unique feature of this small brain area is its high sensitivity to down-regulation of an inhibitory G protein by drugs of abuse, we compared G protein levels in postmortem nucleus accumbens with those in seven other brain regions of chronic users of cocaine, methamphetamine, and heroin, and of matched controls. Biochemical changes were restricted to the nucleus accumbens in which concentrations of G(alpha)1 and/or G(alpha)2 were reduced by 32-49% in the methamphetamine and heroin users. This selective responsiveness to these abused drugs implies a special role for the human nucleus accumbens in mechanisms of drug reinforcement and suggests that some features of the drug-dependent state (e.g., tolerance) might be related to inhibition of G(alpha)1-linked receptor activity.
    Journal of Neurochemistry 06/2000; 74(5):2120-6. · 3.97 Impact Factor
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    ABSTRACT: Cognitive impairment has been reported in some chronic users of psychostimulants, raising the possibility that long-term drug exposure might damage brain neuronal systems, including the cholinergic system, which are responsible for normal cognition. We measured the activity of choline acetyltransferase (ChAT), the marker enzyme for cholinergic neurones, in autopsied brain of chronic users of cocaine, methamphetamine, and, for comparison, heroin. As compared with the controls, mean ChAT levels were normal in all cortical and subcortical brain areas examined. However, the two of 12 methamphetamine users, who had the highest brain/blood drug levels at autopsy, had a severe (up to 94%) depletion of ChAT activity in cerebral cortex, striatum, and thalamus. Based on the subjects examined in the present study, our neurochemical data suggest that brain cholinergic neurone damage is unlikely to be a typical feature of chronic use of cocaine, methamphetamine, or heroin, but that exposure to very high doses of methamphetamine could impair, at least acutely, cognitive function requiring a normal nucleus basalis cholinergic neuronal system. Reduced brain ChAT might be explained in part by a hyperthermia-related mechanism as low ChAT levels have also been observed in brain of some patients with neuroleptic drug-associated hyperthermia. Studies of cognitive and brain cholinergic status in high dose users of MA are warranted.
    Molecular Psychiatry 02/1999; 4(1):26-32. · 15.15 Impact Factor

Publication Stats

132 Citations
47.33 Total Impact Points

Institutions

  • 2001–2002
    • Washoe County Medical Examiner's Office
      Reno, Nevada, United States
  • 2000
    • Centre for Addiction and Mental Health
      Toronto, Ontario, Canada
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan