New research conducted in mice identifies a neural pathway crucial to both depression and addiction. Can we treat these problems by simply manipulating this pathway?
brain circuitry concept illustration
Can we influence brain circuitry to treat depression and addiction?

The pleasure and reward system is one of the most important systems governed by the brain.

It spurs us to enjoy the activities that have contributed to our survival as a species, such as eating, drinking, and having sex, so that we feel motivated to pursue them.

The activity of the reward system, however, is also a key factor in various types of addictive behavior.

Now, a team of researchers from the University of Maryland School of Medicine in Baltimore — led by Prof. Scott Thompson, Ph.D. — has discovered that brain regions involved in addiction may also play a role in depression, albeit in an opposite way.

The researchers, who recently published their findings in the journal Nature, identified an increased strength of signals sent between the hippocampus and the nucleus accumbens — two brain regions that form part of the reward system — as a sign of addiction.

“These two parts of the brain are known to be important in processing rewarding experiences,” notes Prof. Thompson. “The communication between these regions is stronger in addiction, although the mechanisms underlying this were unknown,” he adds.

In the current study, the team also tested a new idea, namely whether the same signals grew weaker in people with depression.

“We also suspected that opposite changes in the strength of this communication would occur in depression. A weakening of their connections could explain the defect in reward processing that causes the symptom of anhedonia [a loss of pleasure in usually pleasurable activities] in depressed patients.”

Prof. Scott Thompson

Influencing the reward system

The researchers worked with mice, focusing on the brain circuitry that plays a crucial role in goal-directed behavior and trying to see if they could change its activity.

To do so, the team introduced light-sensitive proteins into the neurons that form part of this circuitry. With this method, the researchers hoped to either block or boost the signals between the hippocampus and the nucleus.

In the mice that had received the light-sensitive protein, the researchers first created a false reward memory by exposing them to light for 4 seconds. This meant that the mice now associated pleasure with the location of the light exposure.

Essentially, the technique activated the pathway between the two regions and boosted the signals transmitted between them.

After 1 day, the researchers returned the mice to the places where they had received the false reward memory, then exposed them to light again. This time, however, the goal was to shut down signaling between the hippocampus and the nucleus accumbens.

Following this experiment, the investigators confirmed that this pathway is crucial in reward association. Once the pathway was silenced, the mice stopped favoring the location in which they had received the reward memory.

Having established that they could alter the signaling of the reward pathway, the researchers shifted their focus to mouse models of depression.

They tried the same technique, hoping to boost the relevant brain activity in depressed mice, but this time, the experiment did not succeed.

The researchers could only boost the activity of the reward system circuitry after first administering anti-depressant drugs to the rodents. This step allowed the investigators to “imprint” artificial reward memories in the brains of this group of mice as well.

“These exciting results bring us closer to understanding what goes wrong in the brains of clinically depressed patients,” comments the dean of the University of Maryland School of Medicine, Dr. E. Albert Reece, who was not involved in the research.