The Neuroscience of Seeking Pleasure and Avoiding Pain 

Researchers at Cold Spring Harbor Laboratory (CSHL) have zeroed in on the ventral pallidum (VP), an information-processing hub in the brains of mice to discover how VP neurons influence animals' motivation to either seek pleasurable experiences or avoid negative ones.

Source: Li lab/CSHL, 2019

A new state-of-the-art mouse study from Cold Spring Harbor Laboratory (CSHL) used optogenetics to zero in on a specific brain region called the ventral pallidum (VP) that appears to drive an animal's motivation to seek pleasure or avoid pain. These findings (Stephenson-Jones et al., 2019) were published on December 31 in the journal Neuron.

As a 20th-century neuroscientist, my father investigated how Thorndike's Law of Effect—which posits that all animals (including humans) are hardwired to seek pleasure and avoid pain—played out in the brain.

Decades ago, he conducted animal experiments designed to identify specific hormones and neurotransmitters that drove mammals to avoid pain and motivated them to seek pleasure. Dad also helped me understand how the Law of Effect plays out in daily life and served as the medical expert for my first book.

Two neurotransmitters I focused on in The Athlete's Way (2007) were GABA and glutamate. As I described it, "There's a neurotransmitter called glutamate that sears synapses together after a traumatic experience. This is how fear conditioning and avoidance learning become hardwired. Glutamate bonds are hard to dissolve."

GABAergic and Glutamatergic VP Neurons May Drive Opposing Motivational Behaviors

When I wrote about the neuroscience of seeking pleasure and avoiding pain in 2007, we knew much less about how GABA and glutamate work in the brain than we know today.

CSHL Professor Bo Li and colleagues monitored the activity of individual brain cells and confirmed those cells' identities with a flash of light. After training mice to associate certain sounds with either a sip of water or a puff of air, they monitored neural activity in the ventral pallidum. Neurons that used the neurotransmitter GABA to dampen activity in the circuit influencing motivation were important in motivating the mice to seek a water reward. The neurons that used the neurotransmitter glutamate to excite the brain circuit were essential for avoiding the air-puff punishment.

Source: Li lab/CSHL, 2019

As you can see in the diagram and caption above, Bo Li and colleagues recently discovered that GABAergic "reward neurons" and glutamatergic "punishment neurons" in the VP influence an animal's motivational drive to seek pleasure or avoid pain, respectively.

GABA appears to drive pleasure-seeking behavior, while glutamate reinforces avoidance learning designed to avoid pain. The authors sum up the main takeaway of their research: "Here we show that GABAergic and glutamatergic VP neurons selectively control behavior in opposing motivational contexts."

In a positive motivational context, GABAergic VP neurons appear to drive physical movements that result in a reward. On the flip side, glutamatergic VP neurons appear to drive movements (or lack thereof) associated with fight-flight-or-freeze behaviors to avoid pain or punishment.

Does the Motivation to Seek Pleasure or Avoid Pain Have Mental Health Implications?

The latest research from the Bo Li Lab suggests that an imbalance between the push-pull of GABAergic and glutamatergic VP neurons skews "positive vs. negative motivation and may explain behaviors associated with psychiatric disorders like depression or anxiety."

People suffering from major depressive disorder (MDD) are often unmotivated to seek out things that once gave them pleasure. Those of us who are prone to generalized anxiety disorder (GAD) often go to extreme lengths to avoid situations that seem threatening.

Interestingly, if a mouse in this study was really thirsty, it would endure some pain to obtain rewarding sips of water. In situations in which pain was required to receive a reward, both sets of neurons responded.

"The balance between signals that either inhibit or excite VP neurons appears critical in controlling which motivation an animal acts on," Li said in a news release. "Behavioral changes in people with depression or stress-induced anxiety may be caused by changes in this circuit."

By shifting the balance of activity between GABAergic and glutamatergic neurons in the ventral pallidum using optogenetics, the researchers could alter motivational behaviors.

These findings in mice represent the first step toward a better understanding of how specific neurons in the VP influence motivational behaviors in animals. The next step is to study how VP neurons affect human behavior, especially in those with psychiatric disorders.

Note: The final section of this post filters the latest research on the neuroscience of seeking pleasure and avoiding pain through the lens of my life experience.

The Pros and Cons of Training Your Brain to Ignore Painful Warning Signs

As an ultra-endurance athlete, I made myself a human guinea pig in my own "Law of Effect" experiments. Every day, I practiced different ways to override pain while pursuing the reward of finishing a grueling workout or winning a race.

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Most of my competitors in ultra-endurance events would stop pushing themselves harder when the pain of physical exertion became unbearable. When they gave up, I'd go harder. I had a chip on my shoulder and was maniacally driven to prove that I was "tougher than the rest"—no matter how much it hurt.

With 20/20 hindsight, it's clear that one reason I worked so hard never to seem "wimpy" stemmed from being a gay teen who was labeled a "sissy." In the early 1980s, when I was trapped at a homophobic boarding school, I suffered from crippling anxiety and had a major depressive episode (MDE). As a coping mechanism, I started jogging and mastered the art of turning put-downs into motivational rocket fuel. In the 1990s, I became a triathlete.

Source: Christopher Bergland

Through dedicated practice, I learned how to "flip the script" in ways that allowed my brain to cope with ridiculous amounts of self-inflicted "punishment" in the form of running, biking, and swimming extreme distances.

For example, in 2004, I broke a Guinness World Record by running six back-to-back marathons on a treadmill. In the early 2000s, I won the Triple Ironman (7.2-mile swim, 336-mile bike, 78.6-mile run) three years in a row.

After reading about the new research (2019) from the Bo Li Lab at CSHL, I realize that my daily training as an endurance athlete may have tweaked the opposing contributions of GABAergic and glutamatergic ventral pallidal neurons in ways that affected my motivation to seek pleasure and avoid pain.

Disclaimer: Although high levels of exercise may be OK for most people's hearts, overriding the Law of Effect as an athlete can be dangerous. (See "The Dark Side of Mythic Quests and the Spirit of Adventure.")