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Enhancing activity of marijuana-like chemicals in brain helps treat

other," said Kreitzer.

Dopamine appears to modulate these two circuits in opposite ways. When dopamine is depleted, it is thought that the pathway responsible for inhibiting movement becomes overly activated - leading to the difficulty of initiating motion, the hallmark of Parkinson's disease.

Current treatment for Parkinson's includes drugs that stimulate or mimic dopamine. It turns out that the neurons Kreitzer identified as inhibiting motion had a type of dopamine receptor on them that the other cells didn't. The researchers tested a drug called quinpirole, which mimics dopamine, in mice with a condition similar to human Parkinson's disease, resulting in a small improvement in the mice.

"That was sort of expected," said Malenka. "The cool new finding came when we thought to use drugs that boost the activity of endocannabinoids." Based on prior knowledge of endocannabinoids and dopamine, they speculated that the two chemicals were working in concert to keep the inhibitory pathway in check.

When they added a drug that slows the enzymatic breakdown of endocannabinoids in the brain - URB597, being developed by Kadmus Pharmaceuticals in Irvine, Calif. - the results were striking.

"The dopamine drug alone did a little bit but it wasn't great, and the drug that targeted the enzyme that degrades endocannabinoids basically did nothing alone," Kreitzer said. "But when we gave the two together, the animals really improved dramatically."
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Source:Stanford University Medical Center


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