Although methamphetamine (MA) is significantly abused in the U.S., information on the effects of the drug on the brain is largely limited to animal studies. The extent to which the results of animal studies generalize to the human is not known. Broad objective. Our broad objective is to identify those changes in brain of human chronic users of MA which may be responsible for the behavioural and possible neurotoxicological consequences of long-term drug exposure.
Specific aims. During the previous funding period, we demonstrated neurochemical changes in autopsied brain of human MA users suggesting that MA may produce alterations in a dopamine receptor-linked pathway and might cause oxidative stress. Our major specific aims are to establish whether dopamine receptor-modulated adenylyl cyclase activity is altered and whether levels of indices of oxidative stress and damage are increased in brain of human MA users. Design. Neurochemical indices will be measured in autopsied brain of chronic MA users, a matched control group, and in brain of users of cocaine and users of heroin as disease control groups. Health relevance: We expect that our investigation, utilizing, to our knowledge, the only collection of autopsied human brain specimens from long-term MA users, will provide unique and important information relevant to the behavioural effects of chronic MA exposure in the human. It is also important to know whether MA causes oxidative stress and damage in human brain. Ultimately, these data may contribute to the development of new approaches to the problem of drug addiction.
| Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna et al. (2018) Normal glutathione levels in autopsied brain of chronic users of heroin and of cocaine. Drug Alcohol Depend 190:20-28 |
| Tong, Junchao; Ang, Lee-Cyn; Williams, Belinda et al. (2015) Low levels of astroglial markers in Parkinson's disease: relationship to ?-synuclein accumulation. Neurobiol Dis 82:243-253 |
| Tong, Junchao; Fitzmaurice, Paul; Furukawa, Yoshiaki et al. (2014) Is brain gliosis a characteristic of chronic methamphetamine use in the human? Neurobiol Dis 67:107-18 |
| Pifl, Christian; Kish, Stephen J; Hornykiewicz, Oleh (2012) Thalamic noradrenaline in Parkinson's disease: deficits suggest role in motor and non-motor symptoms. Mov Disord 27:1618-24 |
| Tong, Junchao; Furukawa, Yoshiaki; Sherwin, Allan et al. (2011) Heterogeneous intrastriatal pattern of proteins regulating axon growth in normal adult human brain. Neurobiol Dis 41:458-68 |
| Kish, S J; Fitzmaurice, P S; Chang, L J et al. (2010) Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study. J Psychopharmacol 24:281-4 |
| Kish, Stephen J; Fitzmaurice, Paul S; Boileau, Isabelle et al. (2009) Brain serotonin transporter in human methamphetamine users. Psychopharmacology (Berl) 202:649-61 |
| Frankel, Paul S; Alburges, Mario E; Bush, Lloyd et al. (2008) Striatal and ventral pallidum dynorphin concentrations are markedly increased in human chronic cocaine users. Neuropharmacology 55:41-6 |
| Kish, Stephen J; Tong, Junchao; Hornykiewicz, Oleh et al. (2008) Preferential loss of serotonin markers in caudate versus putamen in Parkinson's disease. Brain 131:120-31 |
| Frankel, Paul S; Alburges, Mario E; Bush, Lloyd et al. (2007) Brain levels of neuropeptides in human chronic methamphetamine users. Neuropharmacology 53:447-54 |
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