Regional distribution of methamphetamine in autopsied brain of chronic human methamphetamine users

Kalasinsky, Kathryn S.; Bosy, Thomas Z.; Schmunk, Gregory A.; Reiber, Gregory D.; Anthony, Robert M.; Furukawa, Yoshiaki; Guttman, Mark; Kish, Stephen J.

doi:10.1016/s0379-0738(00)00368-6

Cited by 74 publications

(54 citation statements)

References 8 publications

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“…Drug histories and other subject information have been previously reported (Wilson et al, 1996;Kalasinsky et al, 2001;Moszczynska et al, 2004). Dopamine levels in the caudate also have been reported previously for all of the METH cases (Wilson et al, 1996 andMoszczynska et al, 2004).…”

Section: Subjects and Brain Materialsmentioning

confidence: 59%

Brain levels of neuropeptides in human chronic methamphetamine users

et al. 2007

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SummaryAnimal data show that neuropeptide systems in the dopamine-rich brain areas of the striatum (caudate, putamen, and nucleus accumbens) are influenced by exposure to psychostimulants, suggesting that neuropeptides are involved in mediating aspects of behavioral responses to drugs of abuse. To establish in an exploratory study whether levels of neuropeptides are altered in brain of human methamphetamine users, we measured tissue concentrations of dynorphin, metenkephalin, neuropeptide Y, neurotensin, and substance P in autopsied brains of 16 chronic methamphetamine users and 17 matched control subjects. As expected, levels of most neuropeptides were enriched in dopamine-linked brain regions such as the nucleus accumbens and striatum of normal human brain. In contrast to animal findings of increased neuropeptide levels following short-term methamphetamine exposure, striatal neuropeptide concentrations were either normal or moderately decreased in the methamphetamine users. In other examined dopamine-poor cortical and subcortical brain areas, neuropeptide levels were generally either normal or variably reduced. Although the neuropeptide differences might be explained by methamphetamine-induced damage to neuropeptidecontaining neurons, our human data are consistent with the possibility that, at least in the human striatum, long-term methamphetamine exposure leads to an adaptive process that is distinct from that which increases neuropeptide levels after acute methamphetamine exposure.

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Section: Subjects and Brain Materialsmentioning

confidence: 59%

Brain levels of neuropeptides in human chronic methamphetamine users

et al. 2007

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“…Kish, unpublished data) cerebellar cortex. Given that MA is homogeneously distributed throughout the post mortem brain (including cerebellar cortex) of the MA users (Kalasinsky et al, 2001), the animal and human post mortem data showing partial dopamine selectivity of changes in lipoperoxidation markers point toward the involvement of dopamine as a factor involved in promoting lipoperoxidation (e.g., MA-induced formation of dopamine-derived oxyradicals; Davidson et al, 2001). Although dopamine levels are very low and similar in frontal and cerebellar cortices (S. J. Kish, unpublished data) (Scatton et al, 1983), our finding that aldehyde levels were substantially elevated in frontal cortex but not in the cerebellar cortex could be explained by a more intense dopaminergic innervation of cerebral cortex (Melchitzky and Lewis, 2000;Swanson et al, 2006), although the question of cerebellar cortical innervation seems not to have been resolved in the human (Olsson et al, 1999;Melchitzky and Lewis, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Drug histories and patient information are summarized in Table 1, with the information having been previously reported (Wilson et al, 1996;Tong et al, 2003;Moszczynska et al, 2004). The regional distribution of MA and its metabolite amphetamine in autopsied brain has been reported for 12 of the 16 MA cases (Kalasinsky et al, 2001). Dopamine levels in the caudate have been reported for all of the MA cases (see Table 1 and Moszczynska et al, 2004).…”

Section: Methodsmentioning

confidence: 99%

“…Levels of drugs of abuse in blood and other bodily fluids were measured by the local medical examiner, whereas drug analyses in brain and hair samples were conducted at the Armed Forces Institute of Pathology (Washington, DC). All MA users met the following selection criteria: presence of MA on toxicology screens in blood, autopsied brain, and, where available, sequential scalp hair samples; absence of any other drugs of abuse in these tissues (and absence of blood ethanol); evidence from the case records and structured interviews with medical exam- Wilson et al (1996), Kalasinsky et al (2001), Tong et al (2003), and Moszczynska et al (2004). iner investigators, next of kin, and informants, of use of MA for at least 1 year before death; and absence of neurological illness or brain pathology unrelated to use of the drug.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we showed that levels of MA plus its metabolite amphetamine ("total MA levels") are homogenously distributed throughout the post mortem brain of chronic MA users (Kalasinsky et al, 2001). To establish whether aldehyde concentrations might have been influenced by the amount of MA recently taken, correlations (Spearman) were made between levels of aldehydes in the three brain regions examined and MA plus amphetamine concentrations in the occipital cortex.…”

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confidence: 99%

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Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Fitzmaurice

Tong²,

Yazdanpanah³

et al. 2006

J Pharmacol Exp Ther

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Animal studies suggest that the widely used psychostimulant drug methamphetamine (MA) can harm brain dopamine neurones, possibly by causing oxidative damage. However, evidence of oxidative damage in brain of human MA users is lacking. We tested the hypothesis that levels of two "gold standard" products generated from lipid peroxidation, 4-hydroxynonenal (one of the most reactive lipid peroxidation aldehyde products) and malondialdehyde, would be elevated in post mortem brain of 16 dopamine-deficient chronic MA users compared with those in 21 matched control subjects. Derivatized aldehyde concentrations were determined by gas chromatography-mass spectrometry. In the MA group, we found significantly increased levels of 4-hydroxynonenal and malondialdehyde in the dopamine-rich caudate nucleus (by 67 and 75%, respectively) and to a lesser extent in frontal cortex (48 and 36%, respectively) but not in the cerebellar cortex. Approximately half of the MA users had levels of 4-hydroxynonenal falling above the upper limit of the control range in caudate and frontal cortex. A subgroup of MA users with high brain drug levels had higher concentrations of the aldehydes. Our data suggest that MA exposure in human causes, as in experimental animals, above-normal formation of potentially toxic lipid peroxidation products in brain. This provides evidence for involvement of oxygen-based free radicals in the action of MA in both dopamine-rich (caudate) and -poor (cerebral cortex) areas of human brain.

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Amphetamine and Methamphetamine

Barceloux

2012

Medical Toxicology of Drug Abuse

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Regional distribution of methamphetamine in autopsied brain of chronic human methamphetamine users

Cited by 74 publications

References 8 publications

Brain levels of neuropeptides in human chronic methamphetamine users

Brain levels of neuropeptides in human chronic methamphetamine users

Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Amphetamine and Methamphetamine

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