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Researchers have known for a long time that the neurotransmitter dopamine plays a vital role in the brain. It shuttles between neurons at the synapses, carrying information and instructions about such things as motor control, pleasure and addictive cravings. All human uses and abuses of this chemical have either manipulated its release from nerve cell membranes or its uptake by dopamine transport protein (DAT). Now, however, a group of Boston University researchers has uncovered a completely novel means of dopamine use in the brain. This usage is implicated in Parkinson's, a neurodegenerative disease, and is susceptible to treatment with Zyban and other well-known antidepressant drugs. The findings appear in today's Science.
Neurons release dopamine in a surprising way deep in the substantia nigra, a brain region that governs motor control. There are almost no synapses there, only densely packed cell bodies and sinuous dendrites (the connective tissue of neurons)¿both of which lack the structures needed to release dopamine. While indirectly stimulating sections of substantia negra from rats, though, the Boston group found that the tissue released dopamine anyway. In an elegant series of experiments, they showed that DAT¿the same protein that assiduously removes dopamine at the synapses¿releases it from dendrites. More importantly, they discovered that a DAT inhibitor would quickly eliminate all the extracellular dopamine in the substantia nigra. The same drugs cause a glut of extracellular dopamine at the synapses. In the substantia nigra, a glut of dopamine is fatal for the densely packed cell bodies of neurons.
Parkinson's takes its terrible toll by killing the motor-control neurons of the substantia nigra, but it begins by overexciting brain cells called subthalmic afferents. The Boston University researchers used the same cells to stimulate dopamine release in the substantia nigra, thereby mimicking the pathology of Parkinson's even as they uncovered it. Though this research doesn't point the way to disrupting that first step, it shows how doctors might prevent dopamine from flooding the substantia nigra and destroying the motor-control center of the brain. Zyban and Ritalin (and cocaine) are efficient and well-understood DAT inhibitors. By using these drugs in the early stages of Parkinson's, the scientists hope that the disease can be halted.
