Human Neurochemical Pathology Laboratory

Section Head

Dr. Stephen Kish

Contact 

Dr. Stephen Kish
Human Neurochemical Pathology Laboratory
Centre for Addiction and Mental Health
250 College Street
Toronto, Ontario M5T 1R8
stephen_kish@camh.net

Research Objective 

Our aim is to develop better treatment for patients who have behavioural problems because of brain dopamine “excess” (methamphetamine users) and deficiency (Parkinson’s disease) conditions by understanding the brain neurochemical basis for these disorders. 

Summary of Activities

Preclinical Our preclinical work focuses on neurochemical analyses of the brain of chronic users of the stimulant drugs methamphetamine and ecstasy, and the brain of patients with movement disorders such as Parkinson’s disease and multiple system atrophy. These investigations utilize post-mortem brain and brain scan (by PET) approaches.  To date, we have the world’s only source of autopsied brain material of methamphetamine users for neurochemical analysis. 

Clinical In order to impact on client care, our preclinical efforts are now being translated into clinical pharmacological investigations of new drugs for the treatment of methamphetamine abuse and the behavioural problems associated with chronic dopamine substitution therapy in Parkinson’s disease. 

Research Highlights

1. Moszczynska A, Fitzmaurice P, Peretti FJ, Kalasinsky KS, Furukawa Y, Ang LC, Aiken S, Wickham DJ, Kish SJ. Why is Parkinsonism not a feature of human methamphetamine users? Brain. 224;127:363-370.
   
   Here we report that some chronic users of methamphetamine have dopamine levels as low as those in patients with Parkinson’s disease in a brain region responsible for cognition. This suggests that dopamine substitution therapy might improve cognition in the methamphetamine user during drug withdrawal and thereby increase the likelihood of retention in drug rehabilitation.
   
   
2. Tong J, Hornykiewicz O, Kish SJ. Identification of a noradrenaline-rich subdivision of the human nucleus accumbens. Journal of Neurochemistry. 2006;96:349-354.
   
   Our finding of strikingly high levels of noradrenaline in a part of the brain considered to be involved in responding to both rewarding and aversive stimuli warrants a re-evaluation of the limited role of brain noradrenaline in human brain function, which, over the past 30 years, has focused primarily on an involvement in general brain arousal.
   
   
3. Fitzmaurice P, Tong J, Yazdanpanah M, Liu PP, Kalasinsky KS, Kish SJ. Levels of 4-hydroxynonenal and malondialdehdye are increased in brain of human chronic users of methamphetamine. J Pharmacol Exp Therap. 2006;319:703-9.
   
   This is the first evidence that chronic methamphetamine exposure can cause oxidative brain damage in the human.
   
   
4. Tong J, Hornykiewicz O, Kish SJ. Inverse relationship between brain noradrenaline and dopamine loss in Parkinson’s disease: A possible neuroprotective role for noradrenaline. Archives of Neurology. 2006;64:1724-8.
   
   These postmortem brain observations support the suggestion, based on animal model data, that pharmacological efforts to increase brain noradrenaline might slow down the progression of Parkinson’s disease.

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