Drugs, depression and molecular ferries.

Three teams of neurobiologists have characterized two types of nerve-cell proteins implicated in drug addiction and depression. Their findings, described in the Oct. 25 SCIENCE, may contribute to a better understanding of how stimulants, such as cocaine, and some antidepressant drugs affect the brain, according to the researchers.

The investigators focused on so-called transporter molecules, which serve a ferrying function in the brain. After neurotransmitters deliver a chemical message from one nerve cell to another, specific transporter proteins cart them back to their cells of origin. Drugs such as cocaine block the activity of some transporter molecules, creating a surplus of a particular neurotransmitter in the junctions between the nerve cells.

Two research groups -- one led by Shoichi Shimada of the National Institute on Drug Abuse in Baltimore, the other by John E. Kilty at Yale University -- isolated from rat brains the DNA sequences used by nerve cells to make transporter proteins that target the neurotransmitter dopamine. The researchers then inserted the DNA sequences into lab-grown cells, causing the cells to make dopamine transporters. When they exposed cells containing the dopamine transporters to cocaine and to dopamine-sensitive antidepressants, such as desipramine, the drugs significantly reduced the transporters' ability to take up dopamine.

Scientists believe dopamine influences pleasure-seeking behaviors.

The researchers also found that the dopamine transporters strongly resemble two other transporter molecules previously identified in rat brains by other investigators. One of these ferries the neurotransmitter gamma-aminobutyric acid (GABA) back to the cells that released it; the other handles norepinephrine.

In a separate study of rat brains, a team led by Beth J. Hoffman of the National Institute of Mental Health in Bethesda, Md., identified and characterized a serotonin transporter. Serotonin helps to regulate emotions.

In lab tests, cultured cells inserted with DNA sequences for making serotonin transporters displayed an ability to take up excess serotonin in the same way as brain cells, Hoffman and her co-workers report. But this activity dropped sharply when the experimenters exposed the same cells to antidepressants that block serotonin uptake, including the drug fluoxetine, better known as Prozac.

The researchers note that a comparable response occurred with exposure to amphetamines and related drugs that alter serotonin transmission, such as the appetite suppressant fenfluramine.