Mount Sinai researchers have identified a new receptor complex in the brain that responds to several types of antipsychotic drugs used to treat schizophrenia and also reacts to hallucinogenic drugs such as LSD.
Stuart Sealfon, MD, Professor of Neurology and Director of the Center for Translational Systems Biology at Mount Sinai School of Medicine and colleagues discovered the receptor complex, which could help provide new treatments for schizophrenia and other diseases associated with psychosis. This new study was published online in Nature.
"The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. The discovery of this receptor complex could provide a new target for developing drugs to treat schizophrenia," said Dr. Sealfon.
The study done in mice identified that the two receptors, neurotransmitters glutamate and serotonin, interact and work as a hybrid complex. Hallucinogenic drugs, such as LSD and psilocybin, act at serotonin receptors to cause responses similar to some of the core symptoms of schizophrenia. The researchers showed that the glutamate receptor interacts with the serotonin receptor to form functional complexes in brain cortex. This receptor complex triggers unique cellular responses when targeted by hallucinogenic drugs.
Activation of the glutamate receptor blocks hallucinogen-specific signaling and changes behavioral responses in mice.
In untreated schizophrenics, the serotonin receptor is up-regulated and the glutamate receptor is downregulated, a pattern that could predispose to psychosis. These findings suggest that the newly identified serotonin/glutamate complex may be involved in the altered cortical processes of schizophrenia.
"The findings further our understanding of how hallucinations occur. They suggest a brain abnormality that may contribute to the abnormal brain function in schizophrenia," said Dr. Sealfon. "We can now use this information to do further study and hopefully develop more specific drug therapies for treating patients who suffer from hallucinations and psychosis."
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