“I generally avoid temptation unless I can’t resist it.”
― Mae West
Modern Western medicine devotes many resources to treating the consequences of poor decisions. As a society, we are becoming less physically active and much more sedentary whilst at the same time consuming more and more ultra-processed food. With an estimated 80% of all teenagers and almost 30% of all adults qualifying for couch potato status, the impact of this trend on global health is alarming. It seems an evolutionary arc destined to end with us devolving into a Jabba “The Pizza” Hutt physique. This deadly 1-2 combination is a widely recognized major contributor to the development of chronic disabilities and diseases and is clearly identified as a “global health problem.”[1]
For a solution beyond a lifetime of pharmaceuticals, the key lies in our hands- quite literally. Our behaviors and the choices we make play a crucial role in our health. Why do we choose to do what we do – or, in some cases, don’t do? What draws us to the bright neon of a fast-food restaurant and right past the gym doors? It fuels that classic wry observation, “I joined the gym five months ago, and I haven’t noticed any difference. Tomorrow I’m going to head down there in person and see what’s going on!”
It raises the question: How do we resist temptation?
A recent study has provided some fascinating insights into this age-old question. The study delved into the labyrinth of our minds, decoding how we make value-based decisions, like choosing between a sweet treat and a hard sweat. The research involved placing mice in the center of a maze and allowing them to choose between eight different but equidistant arms. At the end of one path was an exercise wheel. At the end of another corridor was regular old mouse chow. The other routes led to a dark area, a light area, an empty area, or other neutral objects like water. In this model, the mice split most of their time between the exercise wheel and eating standard chow.
Then the empty hallway was replaced by one offering the mouse equivalent of a fast-food drive-through known experimentally as an offering of highly palatable food (HPF). In a fascinating display, when the HPF was available, the mice substantially reduced the amount of time eating standard chow, but the amount of time they engaged in exercise, running on their wheel, remained unchanged. This behavior persisted no matter how long the experiment was run. Thus, the researchers were able to demonstrate that in this mouse model, the voluntary wheel exercise activity was resistant to the “temptation” of chucking it all and just gorging on HPF. This is known as a temptation-resistant voluntary exercise or TRVE.
The researchers then disrupted a group of neurons located in the lateral hypothalamus of the brain. These particular neurons are known as hypocretin orexin neurons (HONs), and they exist in both humans and mice. It is hypothesized that they play the same role in decision-making for humans as they do for mice. When the chemical messenger orexin was blocked, the TRVE was abolished. This was true for both male and female mice.
When orexin was blocked, and HPF was present, mice left the wheel for the meal. This provides some evidence for a level of value-based decision-making, particularly in the setting of competing choices, both of which provide a dopamine surge. It adds a level of complexity to the information processing because the “primary role of the orexin system is not to control how much the mice move or how much they eat; rather, it seems central to making the decision between one and the other, when both options are available,” according to lead researcher Prof. Denis Burdakov.
- The study utilized a murine model in which the mice were subjected to an 8-arm maze, representing a multiple-choice environment.
- The mice were initially given a choice within each of the eight arms consisting of an exercise wheel, an empty corridor, a lit environment, a dark environment, a novel object, water, standard mouse chow, or a novel mouse.
- In the above version, the mice spent most of the time split between the wheel and the standard mouse chow.
- The mice were then subjected to a modified maze in which the previously empty corridor door was replaced by highly palatable food (HPF).
- In this version, the mice spent most of their time split between the wheel and HPF; the mice did not significantly decrease their exercise time but replaced the standard mouse chow with HPF.
- Thus, the affinity for the mice to continue to exercise in the wheel despite the ‘temptation’ of the HPF allows it to be classified as a temptation-resistant voluntary exercise (TRVE).
- The mice then underwent intervention by blocking the actions of the neuropeptide orexin released from the neurons of the lateral hypothalamus area of the brain.
- By blocking orexin, the behavior of the mice was changed to where they did not exercise but instead spent the majority of their time eating HPF.
Caveat:
This study examined the effect of HONs and orexin on decision-making between two pleasure-producing (both exercise and eating cause the release of dopamine) alternatives. In this study, “HONs promote TRVE by decreasing HPF visit duration when the running wheel is available.” It is interesting that orexin only appears to play a role when there is a choice to be made. It is not in and of itself a promoter nor inhibitor of physical activity or of eating; “Rather, the results suggest that orexin arbitrates between eating and running, without influencing appetitive or consummatory drives toward either.” It creates a system whereby the behavioral effects are context-dependent.
While this opens the door to an entirely new level of understanding with important personal and public health implications, it could also be a Pandora’s pillbox. The very popular semaglutides (GLP-1 agonists) act in the hypothalamus, where they are believed to impact behavior by reducing feelings of hunger and increasing feelings of satiety. Some research suggests involvement in the dopamine-related pathways of the nucleus accumbens and the hypothalamus. The long-term effects of this type of pharmacologic alteration on human behavior and health are unknown. New drugs (already being discussed) targeting the orexin biochemical pathway have the potential to put fresh bullets into the behavioral chambers of our minds. The result being drugs prescribed to make us exercise. It seems a bit of an Orwellian Dr. Strangelove approach. Solving global obesity through pharmaceutical Russian roulette is a game the House always wins.
[1] (WHO, 2022)
The Study:
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