Discovery of new receptor complex in brain - better understanding of how hallucinations occur

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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The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation's oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.

Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.