A study looking at the brains of living mice suggests that for nearly 70 years we have always Our design targets the wrong neurons antipsychotic.
Unraveling the vast web of brain cells and figuring out how drugs act on them is a daunting task. A team of researchers led by Northwestern University neuroscientist Sung-sik Yun used a miniature microscope and fluorescent tags to show that an effective antipsychotic drug attaches to a different type of brain cell than what scientists originally thought. I discovered.
Similar to studies suggesting that depression may not be a chemical imbalance in serotonin levels, if widely used antipsychotics target different neurons than expected, treatment for schizophrenia We may need to rethink our understanding of
“There is an urgent need to understand the neural circuits that drive psychosis and how they are affected by antipsychotic drugs,” said Yoon et al. write in a published paper.
Jones Parker as neuroscientist and lead author of the study Said wired According to Max G. Levy, most antipsychotic drugs, including chlorpromazine, first approved in 1954, were discovered by chance. “So we don’t know what effect they actually have on the brain.”
Upon discovering them, scientists became aware of drugs that inhibited them. common symptoms of schizophrenia such as Mania, hallucinations, and delusions appear to act on the brain’s dopamine system.
These antipsychotics inhibit dopamine transmission between brain cells, they learned, and the most potent are compatible with a specific type of dopamine receptor labeled D2.
Brain cells called spinous neurons cluster in and extend out. striatum Expresses either D1 or D2 receptors in the brain. Unlike D1 receptors that excite the brain’s dopamine system, D2 receptor keep quiet that.
By linking the efficacy of antipsychotics to D2 receptors, in schizophrenia the striatum dopamine overflowa chemical imbalance that antipsychotics help correct.
However, new drugs specifically designed to target the D2 receptor Did little to alleviate psychosis. And because no one had actually tested whether the decades-old antipsychotic drug preferentially binds to D2 receptors in animal models of psychosis, its exact mechanism of action remained unknown. Ta.
To investigate, Yoon, Parker, and their team injected mice with one of four drugs used to treat psychosis to see how the animals behaved and how their brain cells behaved. was observed to respond to
They found that two older but effective antipsychotics, haloperidol and olanzapine, had some effect on D2 spiny neurons, but their interaction occurred mainly in D1 neurons. did.
Clozapine is a potent new antipsychotic drug with few side effects that bypasses D2 neurons and overwhelmingly suppresses D1 cells, “which may somehow explain its clinical superiority, especially for treatment-resistant schizophrenia. It’s possible, the researchers said. To tell.
Meanwhile, MP-10, a drug candidate that failed clinical trials for schizophrenia, remained attached to D2 neurons. In fact, MP-10 made her abnormal D1 activity even worse.
In other words, the drug’s clinical efficacy was closely related to its interaction with D1 neurons. Drugs that normalize overactive D1 neurons best alleviate psychosis. This is a discovery that completely changes our understanding of these agents.
“These findings provide a new explanation for the efficacy of antipsychotic drugs,” the researchers said. write. They found that D1 spiny neurons, but not D2-expressing cells, “could be a major contributor to psychosis,” and that normalizing their activity was “an important indicator of antipsychotic efficacy.” suggests that it is possible.
While the findings are a blow to decades of research, they help explain why some antipsychotics, such as clozapine, work while others do not. Dopamine must be kept in mind, Neurotransmitters are not the only associated with mental illness.
The findings also offer a glimmer of hope that researchers can turn course and use these new insights to design vastly improved treatments for schizophrenia. Treatment not available immediately.
This research natural neuroscience.
