Vollum Scientists Find New Form of Dopamine Transmission

07/13/04   Portland, Ore.

An Oregon Health & Science University research team has uncovered a novel form of transmission between neurons in the brain that is mediated by dopamine. The neurons are found in parts of the brain associated with movement, substance abuse and mental disorders.

Scientists at the Vollum Institute, OHSU School of Medicine, reported in a study published in the journal Neuron that the neurotransmitter dopamine is released from midbrain nerve cells in a much more precise, targeted manner than previously thought.

They discovered that dopamine molecules are released as packages from stores, or vesicles, in branch-like extensions of neurons called dendrites. The dopamine travels to dopamine receptors on tiny terminals within milliseconds. Until now, scientists had only detected the release of dopamine in the midbrain and suspected that the neurotransmitter was dispersed over wide areas to reach receptors.

"We've demonstrated that this synaptic current is over and done within a second," said John Williams, Ph.D., senior scientist at the Vollum Institute, OHSU School of Medicine, and a study co-author. "We knew dopamine was released in this place, we knew the cells were sensitive to dopamine, but nobody had been able to put the two together."

In addition, the study found that the current is highly sensitive to drugs such as cocaine, which increased the size and duration of the current, and even levodopa, or L-dopa, a drug converted in the brain to dopamine and which enhanced dopamine stores. L-dopa is used clinically to treat Parkinson's disease symptoms.

The study focused on dopamine transmission in the substantia nigra, a part of the midbrain where dopamine cells lose function, leading to Parkinson's disease, and the ventral tegmental area, a region containing dopamine cells involved in the rewarding properties of many abused drugs, such as cocaine, amphetamine, opioids and nicotine.

Researchers believe pinpointing alterations in the system under pathological conditions such as Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder and substance abuse could help them someday identify new therapeutic targets for these conditions.

"We don't know yet what the real significance of this process is going to be down the road," said Michael Beckstead, Ph.D., postdoctoral fellow at the Vollum Institute and the study's lead author. "For now, we're looking at a basic physiological phenomenon."


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