Experimental Small Molecule Shows Potential for Preventing Methamphetamine Relapse

FNew research from The Scripps Research Institute (TSRI) suggests that the reason methamphetamine (meth) users find it so hard to quit—88 percent of them relapse, even after rehab—is that meth takes advantage of the brain’s natural learning process. The TSRI study in rodent models shows that ceasing meth use prompts new neurons to form in a brain region tied to learning and memory, suggesting that the brain is strengthening memories tied to drug-seeking behavior. “New neuronal growth is normally thought of as a good thing, but we captured these new neurons assisting with ‘bad’ behaviors,” said Chitra Mandyam (photo), Ph.D., who led the research as an Associate Professor at TSRI before starting a new position at the Veterans Medical Research Foundation and the University of California, San Diego. The scientists discovered that they could block relapse by giving animals a synthetic small molecule to stop new neurons from forming. This molecule, called isoxazole-9 (Isx-9), also appeared to reverse abnormal neuronal growth that developed during meth use. The new research was published online on March 28, 2017 in Molecular Psychiatry. The article is titled “A Synthetic Small-Molecule Isoxazole-9 Protects Against Methamphetamine Relapse.” Neurons are born all the time in a process called neurogenesis. In a 2010 study, Dr. Mandyam and her colleagues at TSRI showed that increased neurogenesis is tied to a higher risk of drug relapse, but they weren’t sure of the new neurons’ role in the process. The researchers were especially curious about a “burst” of neurogenesis that occurs during abstinence from meth. The new study may explain why the brain is so eager to make neurons during abstinence: meth hijacks the natural neurogenesis process.
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