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April 1, 2009
Updated for print Apr. 6 2009, p. 27

Addiction

Brain Hormone Has Role In Addiction

Blocking hormone receptor could curtail cocaine craving

Sophie L. Rovner

New findings about a peptide produced in the brain might lead to a novel pathway for treating drug addiction.

The peptide is melanin-concentrating hormone (MCH), a natural appetite stimulant. 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 (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0811331106). 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 that these could be tested for treating cocaine addiction.

Sara J. Ward, who studies the impact of opioids, cannabinoids, and other drugs at Temple University, says Civelli's results are significant because "successful pharmacotherapies for cocaine addiction and dependence remain lacking despite years of vigorous research." She adds that previous experimental approaches had undesirable side effects because they targeted biological pathways that were central to other behaviors beyond addiction. MCH blockage may have more subtle effects, Ward says, and therefore might be promising as a treatment for drug addiction if its effects on appetite aren't significant.

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Chemical & Engineering News
ISSN 0009-2347
Copyright © 2009 American Chemical Society

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