Despite the explosive increase in cocaine abuse, little information is available with respect to the effects, in human brain, of long-term exposure to this drug. The major objective of our study is to conduct, for the first time, a systematic and comprehensive examination of the behaviour of the major neurotransmitter systems in autopsied brain of cocaine abusers. We propose to test the Specific Hypothesis that chronic cocaine abuse will be associated with long-lasting depletion in autopsied human brain in the markers for the monoamine neurotransmitters as assessed by HPLC, quantitative autoradiography, receptor binding, and photoaffinity labelling procedures. Autopsied cocaine-abused brain (n=10 per year for the next three years) will be carefully selected from over 250 possible autopsies at one Canadian (Toronto) and two U.S. (Minneapolis; Bronx, N.Y.) centers. The obtained neurochemical data will be compared with biochemical findings obtained in two drug (chronic heroin; alcohol) and one non-neurological group. All of the applicants have demonstrated expertise in the relevant human brain dissection, neurochemical, and neuropathological components of this investigation. Much effort is now being directed to experimental animal studies designed to understand the biochemical basis of cocaine addiction and the long-term changes in brain following chronic cocaine abuse. We argue that such studies should more appropriately be conducted in the human brain. We suggest that the results of our intensive study will provide, for the first time, baseline information with respect to the potential long-term pharmacologic/neurotoxicological efforts of cocaine as well as a springboard for formulating new treatment strategies for the human cocaine abuser.
| 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 |
Showing the most recent 10 out of 14 publications
