Findings Could Lead to New Treatments for Schizophrenia, Parkinson's, Other Diseases
Irvine, Calif. - Researchers at UC Irvine's College of Medicine have discovered how chemicals in the brain that are related to the active ingredient of marijuana help regulate body movements and other motor activity in rats.
In the April issue of the journal Nature Neuroscience, the researchers also report finding a network of these chemicals within the brain that prevents the overactive motor behavior found in schizophrenia, Parkinson's disease and Tourette's syndrome. The discoveries ultimately could result in new treatments for these and other neurological diseases.
Daniele Piomelli, associate professor of pharmacology, and Andrea Giuffrida, a post-doctoral researcher, found that a marijuana-like chemical called anandamide (the Sanskrit word for "bliss") inhibits the effects of nerve cells that transmit dopamine, which is largely responsible for stimulating movement and other motor behavior in the brain. For years, scientists have linked the uncontrolled production of dopamine to schizophrenia, Tourette's syndrome (which causes severe "nervous tics") and Parkinson's disease.
"This shows for the first time how anandamides work in the brain to produce normal motor activity," Piomelli said. "Patients with schizophrenia and other diseases have reported that marijuana appears to relieve some of their symptoms, but scientists have never found a physiological reason why. By understanding how the anandamide system works similarly to marijuana, we can explore new ways to treat these diseases more effectively."
But Piomelli said his research group will not consider marijuana in future research aimed at developing new treatments, because its chemical activity doesn't produce the effects on dopamine that are useful for treating these diseases. "Marijuana doesn't provide the regulatory effects on dopamine in the brain that we're looking for," he said.
The researchers found that anandamide is part of a network of nerve cells in an area of the brain called the striatum, which coordinates all body movements and other motor behavior. In the striatum, the anandamide network inhibited dopamine's attempts to stimulate the body's motor nerves. Normally, nerve cells regulate this behavior by releasing anandamides at the same time they release dopamine. In order to temper the effects of dopamine, the anandamides bind to nerve cell sites called cannabinoid receptors, so-named because they are targets of tetrahydrocannabinol (marijuana's active ingredient) as well as related chemicals like anandamides. When anandamides were bound to these receptors, body movement in the rats decreased.
But when the researchers prevented the cannabinoid receptors from binding to anandamides, the blocked nerve cells could no longer inhibit dopamine's effects. In such a state, the rats experienced severe nervous tics and other uncontrolled motor activity. In humans, such exaggerated activity brought on by unregulated dopamine production can result in diseases such as schizophrenia, Tourette's and Parkinson's.
By enhancing the nerve cells' sensitivity to anandamide, new medicines could treat these diseases without the side effects of current medicines, Piomelli said. "Current drugs certainly halt the actions of dopamine, but the side effects, including sedation and dizziness, are very severe," he said. "Drugs that exploit the anandamide system can provide a gentler way of reducing the hyperactivity in the brain caused by too much dopamine."
But Piomelli said it will be many years before any drugs will be available on the market. "We're just beginning to map out where this system works in rats' brains. We still are a long way from knowing how anandamides work in humans, and any potential drugs would have to be tested rigorously for their effectiveness and safety."
Piomelli's research group discovered the existence of anandamides in the brain and has spent several years exploring how these chemicals and their nerve-cell receptors work in the central nervous system. Piomelli and Giuffrida were assisted in their research by Loren H. Parsons and Toni Kerr at the Scripps Research Institute, La Jolla, Calif., and Fernando Rodriguez de Fonseca and Miguel Navarro of the Universidad Complutense, Madrid.
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