Animal Study Gives Insight To Why Depression and Addiction Treatments Sometimes Don’t Work

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New research published in the journal Neuron may give inside to why drug treatments for addiction and depression are ineffective for some individuals while working on others.

brain wiringResearchers from Washington University School of Medicine in St. Louis say they believe the inconsistent effect is associated with the brain’s reward and aversion pathways.

After observing mice, the team saw brain pathways linked to reward and aversion behaviors are in such close proximity they may unintentionally be activated at the same time. Thus, drug treatments for addiction and depression may simultaneously stimulate reward and aversion responses leading to a net zero effect in some patients.

“We studied the neurons that cause activation of kappa opioid receptors, which are involved in every kind of addiction — alcohol, nicotine, cocaine, heroin, methamphetamine,” said principal investigator Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology.

“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 frequently results when a drug temporarily produces a reward response in the brain that prompts an aversion response signaling the urge for more of the drug once it wears off.

For the study, the researchers studied genetically engineered so that some of their brain cells could be activated with light. The team then used tiny, implantable LED devices to shine a light on the neurons which they used to stimulate cells in a region of the brain linked to a reward response called the nucleus accumbens. The researchers say cells in this area of the brain are spotted with kappa opioid receptors linked to addiction and depression.

The researchers observed that mice returned over and over to the same area of the maze where the researchers would stimulate brain cells to produce a reward response, however activating cells only a millimeter away resulted in significant aversion behavior.

“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,” said first author Ream Al-Hasani, Ph.D., an instructor in anesthesiology.

“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.”

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