Morphine vs. cocaine: A different mechanism of addiction

Morphine and cocaine both lead to addiction in part because of how they affect key reward areas in the brain. But a new study shows that they do this in very different ways -- knowledge that may eventually make treatments for addicts more specific and successful, but that also may complicate matters for people who take multiple drugs at once.

Cocaine and morphine both have profound effects on the flow of dopamine -- a neurotransmitter scientists have consistently implicated in our sensations of reward in the brain. Signaling takes place when one neuron releases dopamine and a neighboring cell takes it up. The excess dopamine left over between the cells is then brought back into the cell that released it, a process called reuptake.

But cocaine blocks reuptake, leading to more dopamine hanging out between cells. That results in a more powerful sense of reward.

This process has been particularly well-studied in two brain areas called the ventral tegmental area, or VTA, and the nucleus accumbens. Neurons that originate in the VTA release dopamine in the nucleus accumbens, which is right next door, and cocaine appears to impact these neurons more than others.

Another chemical called BDNF has been shown to play a key role in cocaine reward by amplifying the addictive nature of cocaine. It does this by supporting changes to the dopamine-sensitive cells in the nucleus accumbens. These changes keep the cells sensitive to cocaine over time.

But in the new study, published Thursday in the journal Science, researchers demonstrate that BDNF actually has the opposite effect when paired with morphine: It decreases morphine’s rewarding effect.

When the scientists used genetic techniques to eliminate BDNF or its receptor molecule from the VTA of mice, morphine suddenly became more rewarding.

It turns out that BDNF’s diluting effect on morphine reward works like turning down a light’s dimmer switch -- it dials down the number of electrical impulses transmitting information between the VTA and the nucleus accumbens. The researchers determined this by directly exciting neurons in the nucleus accumbens -- the ones that receive information from the VTA. This completely eliminated BDNF’s ability to make morphine less rewarding.

The scientists note that, while the mechanism of addiction is different for the two drugs, the pathway is basically the same: Both drugs mess up the signaling between the two brain regions, but through different means. That means researchers should start looking at how chemicals like BDNF influence not just morphine or cocaine abusers -- and their mouse equivalents -- but users of multiple drugs as well.

You can read a summary of the study here.

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