New Haven, Conn. -- A drug that lowers brain levels of the chemical glutamate -- one of the neurotransmitters responsible for relaying messages between neurons -- can reverse symptoms of a rat model of schizophrenia without apparent side effects, according to a Yale University School of Medicine study.
The research, published in the Aug. 28 issue of the journal Science, suggests a possible new class of medications that could be effective in treating schizophrenia and other psychiatric disorders, such as addiction, which are thought to be associated with abnormal glutamate-mediated neurotransmission.
The study was conduced by Bita Moghaddam, associate professor of psychiatry and neurobiology at Yale School of Medicine, and research associate Barbara W. Adams.
Rats under the influence of PCP, a hallucinogen also known as "angel dust" that causes schizophrenia-like symptoms in healthy people, developed symptoms such as frantic running, incessant head-rolling, and disturbances in memory and attention that are thought to parallel symptoms of schizophrenia in humans. By using a drug that stimulates a specific type of glutamate receptor, the Yale researchers succeeded in reversing these behavioral effects of PCP.
The promising new compound used in the Yale study, called LY354740, is being developed by Eli Lilly & Co. in Indianapolis for treating anxiety and other psychiatric disorders. The drug lowered abnormally high levels of glutamate in the PCP-treated rats by stimulating a subgroup of the metabotropic glutamate receptors (mGluRs). As glutamate levels fell, the rats showed improved working memory and reduced locomotion and head-rolling, Moghaddam reported. The drug worked at a dose that did not reduce brain levels of dopamine, an essential neurotransmitter that is the target of existing medications for schizophrenia.