Scientists around the world have been working feverishly with a certain melanin-concentrating hormone (MCH) that works with dopamine in the brain to mediate hunger, hoping to develop anti-obesity medications. Researchers Shinjae Chung and Olivier Civelli of UC Irvine took a slightly different approach and examined how MCH might mediate addictive behavior – and how diminishing MCH in the brain might help cocaine addicts beat their cravings.

The Role of Dopamine and MCH

Dopamine regulates pleasure and pain, including mediating the pleasure we feel when hungry and eating. Dopamine activity from within the nucleus accumbens in the brain plays a known role in the development of addiction and drug cravings.

MCH works with dopamine in the brain to help regulate hunger and food consumption – the more MCH in the brain, the hungrier we feel. Chung and Civelli believed that MCH did more than just regulate hunger, hypothesizing that MCH also influenced the pleasure we feel while eating, with higher levels of neural MCH making eating more pleasurable.

To test this theory, the UC Irvine researchers measured dopamine signaling and found that high levels of MCH increased dopamine interactions within the nucleus accumbens while eating. Increased dopamine signaling in the nucleus accumbens indicates a pleasurable experience.

The Influence of Lowered MCH Levels on Cocaine Cravings

The scientists then examined the impact of varying levels of MCH on cocaine addiction.

Cocaine-dependent mice were found to have higher-than-average baseline levels of MCH in the nucleus accumbens. When the researchers blocked MCH in the brain, cocaine cravings were reduced. Additionally, mice genetically lacking receptors for MCH craved cocaine less than "normal" mice. Thus, MCH seems to play a central role in the continuation of cocaine cravings, and manipulating MCH levels can reduce the intensity of cocaine cravings.

Civelli, a professor of neuropharmacology, said that the research team was optimistic that "efforts to target MCH may lead to new treatments to break addiction to cocaine and, possibly, other drugs, like amphetamines and nicotine."

There is not yet an appropriate or safe mechanism for reducing MCH in the human brain, but researchers have been developing experimental MCH blockers for weight loss applications. Should these prove safe and effective, they could also be used for human trials testing the efficacy of MCH reduction in cocaine addiction treatment.

A Potentially Major Breakthrough

Because dopamine is so central to our experience of pleasure, pain, and muscle movement, experimental cocaine medications that have disrupted dopaminergic activity have come with unacceptably high side effects. Reducing dopamine's influence on cocaine via MCH appears to be much more targeted and therefore less disruptive to other vital dopamine-mediated neural activities. This research, published in the online addition of the Proceedings of the National Academy of Sciences, is particularly noteworthy, because MCH-reducing drugs may work to help cocaine addicts quit without causing significant side effects.