Role of Endogenous Cannibinoids in L-DOPA Dykinesias

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Andrea Giuffrida, Ph.D.
University of California, Irvine, California

Abstract

Many basic science as well as clinical teams are seeking the brain area(s) involved in the production of dyskinesias, the common complication seen in Parkinson patients treated with levodopa. Using evidence that suggests that the brain's cannabinoid receptors (those reacting to the active ingredient in marijuana, among others) when involved, reduce or stimulate motor activity. Dr. Andrea Giuffrida (University of California, Irvine) will study lesioned compared with intact rats, then apply the resultant data to human patients and matched control subjects. He and his group will test the animals using susbstances called neuromodulators, drugs that regulate the activity of the basal ganglia, the area of the brain affected in Parkinson's disease.

Progress Report (as of 3/2003)

What may be the separate or mixed roles of dopamine and cannabinoids in the brain areas most affected by Parkinson’s disease? Dr. Andrea Giuffrida and his colleagues at the University of California, Irvine (long a center for studying degenerative disorders) have used their funding to investigate the cross-talk between naturally-occurring cannabinoids and the dopaminergic system and how this balance is altered by levodopa therapy, leading to motoric side effects such as dyskinesias. Endocannabinoids (naturally-occurring in brain) seem to be important in modulating the dopamine in the basal ganglia. When their receptors are impaired and their signaling decreases, dyskinesias increase. This group has learned that activation of specific receptors may alleviate these motoric effects, at least in 6-OHDA-lesioned rats.

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