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 The National Institute on Drug Abuse (NIDA) is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science to bear on drug abuse and addiction. 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 Antidepressants
Medications prescribed to relieve major depression. Classes of antidepressants include selective serotonin reuptake inhibitors (fluoxetine/Prozac, sertraline/Zoloft), tricyclics (amitriptyline/ Elavil), MAOIs (phenelzine/Nardil), and heterocyclics , such as desipramine desipramine /de·sip·ra·mine/ (des-ip´rah-men) a tricyclic antidepressant of the dibenzazepine class; used as the hydrochloride salt.
a tricyclic antidepressant. , 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 GABA ?.
GABA (gamma-aminobutyric acid)
A neurotransmitter that slows down the activity of nerve cells in the brain. ) back to the cells that released it; the other handles norepinephrine norepinephrine (nôr'ĕpīnĕf`rən), a neurotransmitter in the catecholamine family that mediates chemical communication in the sympathetic nervous system, a branch of the autonomic nervous system. .
In a separate study of rat brains, a team led by Beth J. Hoffman of the National Institute of Mental Health The National Institute of Mental Health (NIMH) is part of the federal government of the United States and the largest research organization in the world specializing in mental illness. 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 fluoxetine /flu·ox·e·tine/ (floo-ok´se-ten) a selective serotonin reuptake inhibitor used as the hydrochloride salt in the treatment of depression, obsessive-compulsive disorder, bulimia nervosa, and premenstrual dysphoric disorder. , better known as Prozac.
The researchers note that a comparable response occurred with exposure to amphetamines Amphetamines
Sympathomimetic amines; sometimes called speed; synthetic chemicals that stimulate the central nervous system.
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amphetamines and related drugs that alter serotonin transmission, such as the appetite suppressant fenfluramine.