New Clues Discovered for Treatment of Parkinson’s and Schizophrenia

Acetylcholine, a neurotransmitter for the human brain, may be one reason why addicts smoke, and could be key to developing new approaches to treatment for schizophrenia and Parkinson’s disease.

Acetylcholine may play a role in the release of dopamine, another one of the brain’s neurotransmitters, and is thought to be important in learning, movement and in reinforcing or rewarding behavior.

In an article published in the December issue of Nature Neuroscience, Dr. John A. Dani, a professor in the neuroscience division at Baylor College of Medicine, says that when dopamine neurons fire in the midbrain, dopamine is released onto the targets in the forebrain.

"It’s just like turning on a garden hose in the back of the house to water plants in the front of the house," Dr. Dani said. "We found that there is a ‘valve’ that controls the hose at the other end. When the faucet is on, the water does not come out of the hose unless the valve is also open, meaning that this valve is controlling the release of dopamine in the target."

Scientists sliced brain tissue in mice, pinpointing the striatum, an area rich with dopamine neurons. A probe was inserted into the brain slice to measure dopamine release. Findings showed that if the nicotinic acetylcholine receptors were inhibited, dopamine release fell by 80 percent, meaning that acetylcholine can control dopamine release.

This sheds new light on tobacco addiction, revealing that not only does nicotine activate dopamine neurons in the midbrain, but it also regulates the release.

"Classically, drugs of addiction such as cocaine, amphetamines and nicotine boost dopamine by turning on the dopamine source. This work shows that there is a very potent control at the other end, in the target," Dr. Dani said.

Researchers hope that these findings will further their understanding and suggest treatments of diseases such as schizophrenia and Parkinson’s disease, both of which involve dopamine systems of the brain.

Dr. Dani said schizophrenics have the highest prevalence of smoking that is found for any grouping of the population.

"Schizophrenics are commonly treated with medications that block dopamine receptors, meaning that dopamine is being released, but the symptoms of the disease are being treated with drugs that block the receptors," Dr. Dani said.

Similarly, this research might hold the possibility for treatment of Parkinson’s disease, a movement disorder in which dopamine neurons have been lost. Patients with the condition are usually treated with L-DOPA, a compound that allows them to make dopamine.

"This research opens up a new avenue for treating neurological and psychiatric diseases in terms of drug therapy with the goal of promoting dopamine release," Dr. Dani said.

- Collaborators include Drs. Fu-Ming Zhou, and Yong Liang.

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