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Biological Chemistry

Blocking Brain Hormone Receptor Curbs Addiction . . .

New findings about a natural appetite stimulant produced in the brain might lead to a novel pathway for treating cocaine addiction

by Sophie L. Rovner
April 6, 2009 | A version of this story appeared in Volume 87, Issue 14

New findings about a natural appetite stimulant produced in the brain—melanin-concentrating hormone (MCH)—might lead to a novel pathway for treating drug addiction (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas. 0811331106). A large amount of the hormone's receptor, MCH1R, is found in a brain region that helps control behaviors associated with reward and motivation. So Olivier Civelli of the University of California, Irvine, reasoned that MCH and its receptor might participate in addiction. In earlier work, Civelli's team screened a chemical library and discovered that a small molecule called TPI 1361-17 could block binding of MCH to its receptor (Eur. J. Pharmacol. 2009, 602, 194). Using this compound, the researchers have now shown that the MCH system helps control addictive behavior in mice and rats. Injections of TPI 1361-17 into the brain of the test animals reduced cocaine use and relapse. TPI 1361-17 apparently doesn't cross the blood-brain barrier, so it's not suitable as an addiction treatment for people. But Civelli says the pharmaceutical industry is developing other MCH1R blockers, mostly for weight-loss applications, and these could be tested for treating cocaine addiction.

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