Rat Studies At Yale University School Of Medicine Suggest A New Class Of Medications For Treating Schizophrenia

August 27, 1998

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.

"By targeting this group of glutamate receptors, we avoided the drawbacks of drugs that appear to produce undesirable side effects by interfering with the normal functioning of dopamine," Moghaddam explained.

Researchers have been searching intensively for a drug that could replace current schizophrenia medications, such as haloperidol, which can have a number of disturbing side-effects, including uncontrollable tremors similar to those in Parkinson's patients. Furthermore, current anti-psychotic drugs offer little relief from other schizophrenia symptoms, such as poor attention spans, jumbled thoughts and difficulty interacting with other people, according to an accompanying "News of the Week" article in the journal Science.

"The metabotropic glutamate receptors could provide important pharmaceutical targets in the treatment of psychiatric disorders associated with increased or decreased glutamate-mediated signaling between neurons," Moghaddam said. She cautioned, however, that the drug might not have the same effect in people, and that PCP-induced symptoms in rats may not accurately reflect symptoms of schizophrenia in humans.

Research was conducted at the West Haven Veterans' Administration Medical Center with funding from the National Institute of Mental Health.
-end-


Yale University

Related Schizophrenia Articles from Brightsurf:

Schizophrenia: When the thalamus misleads the ear
Scientists at the University of Geneva (UNIGE) and the Synapsy National Centre of Competence in Research (NCCR) have succeeded in linking the onset of auditory hallucinations - one of the most common symptoms of schizophrenia - with the abnormal development of certain substructures of a region deep in the brain called the thalamus.

Unlocking schizophrenia
New research, led by Prof. LIU Bing and Prof. JIANG Tianzi from the Institute of Automation of the Chinese Academy of Sciences and their collaborators have recently developed a novel imaging marker that may help in the personalized medicine of psychiatric disorders.

Researchers discover second type of schizophrenia
In a study of more than 300 patients from three continents, over one third had brains that looked similar to healthy people.

New clues into the genetic origins of schizophrenia
The first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, appears in the Jan.

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.

Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.

Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.

The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.

Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.

Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.

Read More: Schizophrenia News and Schizophrenia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.