Brain pathways linked to reward and aversion behaviors are so close together that they could be activated at the same time, even unintentionally.

New research, conducted with mice, suggests that drug treatments for addiction and depression may simultaneously stimulate reward and aversion responses, resulting in a net effect of zero in some patients. Principal investigator Michael R. Bruchas, associate professor of anesthesiology and neurobiology at Washington University School of Medicine in St. Louis, says:

“We studied the neurons that cause activation of kappa opioid receptors, which are involved in every kind of addiction—alcohol, nicotine, cocaine, heroin, methamphetamine.

We produced opposite reward and aversion behaviors by activating neuronal populations located very near one another. This might help explain why drug treatments for addiction don’t always work—they could be working in these two regions at the same time and canceling out any effects.”

Addiction can result when a drug temporarily produces a reward response in the brain that, once it wears off, prompts an aversion response that creates an urge for more drugs.

Maze Return

The researchers studied mice genetically engineered so that some of their brain cells could be activated with light.

Using tiny, implantable LED devices to shine a light on the neurons, they stimulated cells in a region of the brain called the nucleus accumbens, producing a reward response. Cells in that part of the bran are dotted with kappa opioid receptors, which are involved in addiction and depression.

The mice returned over and over again to the same part of a maze when the researchers stimulated the brain cells to produce a reward response. But activating cells a millimeter away resulted in robust aversion behavior, causing the mice to avoid these areas.

Says first author Ream Al-Hasani, an instructor in anesthesiology:

“We were surprised to see that activation of the same types of receptors on the same types of cells in the same region of the brain could cause different responses. By understanding how these receptors work, we may be able to more specifically target drug therapies to treat conditions linked to reward and aversion responses, such as addiction or depression.”

Al-Hasani, Ream et al. Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward Neuron , Volume 87 , Issue 5 , 1063 - 1077 DOI:

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