Is the Brain Wired to Give Up When A Reward Is Out of Reach?

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Few things crush the spirit like the sensation of giving up. We all know the feeling, when you thought a goal was in reach, then realize you just don’t have enough of whatever it takes to get there.

But what if you found out that this feeling of depletion is really just another thing our brain does to keep its chemical symphony in tune?

That’s the conclusion of a new study in mice focused on how the brain musters motivation in pursuit of rewards, and the flip side when the reward is out of reach.

Neuroscience already has a good handle on what happens when we’re excited about pursuing a “reward.” Whether it’s something tangible like money, food or sex, or more abstract like love or power, a similar chemical pattern plays out in the brain. The neurotransmitter dopamine floods neural pathways in what’s often called the brain’s “reward center.” This is the biochemical dynamic that drives us forward, and it’s no exaggeration to say that it’s central to why we pursue anything at all.

But brains are instruments of balance, and as it turns out mammals have another system that exerts a restraining force on the reward surge, called the nociception modulatory system (which also happens to be key to how the brain modulates pain). The neurons in this system (dubbed “frustration neurons”) emit molecules called nociceptin that suppress dopamine. In effect, nociceptin is anti-dopamine.

Researchers discovered how this works by observing mice looking for sugar tucked away in a little port. To get the sugar, they had to poke their snout in and lick. The researchers made it easy at first to spark more motivation to get the goods, but with each attempt, they made it a little harder for the mice to succeed. After making it so hard that the mice poked their snouts over and over and still couldn’t get a taste, they finally started giving up. Eventually, all of the mice stopped trying.

While this was going on, the researchers were tracking the rodents’ neural activity and found that nociceptin neurons were most active when the mice gave up. Not coincidentally, these neurons are located near the brain’s ventral tegmental area (VTA), the hub of activity in the reward center, and the proximity provides easy access to tap the breaks.

"The big discovery is that large complex neurotransmitters known as neuropeptides have a very robust effect on animal behavior by acting on the VTA,” said co-lead author Christian Pedersen, a Ph.D. student in bioengineering at the University of Washington School of Medicine, in a press statement.

The reason for this interplay between reward-surge and reward-suppression comes down to the brain’s tendency toward stability and balance, aka homeostasis. The brains of mammals have built-in mechanisms to keep reward seeking from going too far in either direction. In the wild, continuing to engage in risky reward-seeking behavior when success is out of reach could result in injury or death, so we’ve likely inherited this chemical balancing act as an evolved survival mechanism.

Disorders like depression and addiction may develop from these regulatory systems not working well for any number of reasons. The researchers think the latest study could shed light on those and other disorders, and perhaps eventually lead to the development of new chemical interventions to help restore balance. That will require further replication in humans, of course, but this research is a strong starting point.

"We might think of different scenarios where people aren't motivated like depression and block these neurons and receptors to help them feel better," said senior study author Michael Bruchas, professor of anesthesiology, pain medicine and pharmacology at the University of Washington School of Medicine. "That's what's powerful about discovering these cells. Neuropsychiatric diseases that impact motivation could be improved."

For now, the value of the discovery could be more straightforward, in simply knowing that "giving up" after trying hard isn't a character flaw or moral failure, it's just another way that the brain keeps things level.

The study was published in the journal Cell.

© David DiSalvo