The Dopamine Question That Changes Everything

I was putting together Part 2 of my dopamine series—digging into lifestyle factors, receptor sensitivity, and how modern life exploits our prediction systems—when one of my Substack subscribers, Tom Welsh, dropped an absolute gem of a question in the comments:

“One hard question: if dopamine is necessary for motivation, what determines which behaviour is motivated? Why does dopamine make one person hungry, another keen for a wee dram, a third eager to exercise, and a fourth deeply interested in biochemistry?”

Brilliant. This is precisely the kind of question that cuts through the noise and gets to the heart of how dopamine actually works in the real world.

Because here’s the thing: if you’ve read Part 1, you know dopamine isn’t the “pleasure chemical”—it’s the motivation molecule, the “go get it” signal. But Tom’s question exposes the critical next layer: dopamine is the accelerator, not the steering wheel.

So what determines which behaviours get motivated? Why does the same neurochemical system drive completely different actions in different people—or even in the same person at other times?

Let me break it down.

1. Learning History & Associative Conditioning: Your Brain’s Personal Algorithm

Your brain is a prediction machine. Through repeated experience, it learns what predicts reward, relief, pleasure, or the absence of pain. Dopamine doesn’t create desires—it amplifies the motivational pull toward things your brain has learned are valuable.

Think back to Pavlov’s dogs from Part 1. After repeated pairings of bell and food, the dopamine response shifted backwards in time—it fired at the prediction (the bell), not the reward itself (the food). The dog’s brain encoded the association, and dopamine now marks the anticipation, driving the behavioural response (salivation) before the food even appears.

The same principle applies to humans. If you’ve repeatedly experienced that a dram of whisky relieves stress, soothes anxiety, or provides a warm sense of relaxation, your brain encodes that association. When you encounter stress or the environmental cues that predict drinking (the pub, the bottle, 5 pm on a Friday), dopamine fires in anticipation of that learned reward. You feel the urge—the wanting—before you’ve taken a single sip.

Someone else’s brain learned different associations. Maybe they discovered that a hard run clears their head and makes them feel accomplished. Now, when they’re stressed or see their running shoes, dopamine fires, creating the motivational drive to lace up and go. Same stress, same dopamine system, but entirely different learned prediction.

This is reward-prediction-error learning in action when an outcome is better than expected, dopamine surges, reinforcing the behaviour. When it’s worse than expected, dopamine dips, weakening the association. Over time, your brain builds a personalised map of what’s worth pursuing based on your unique history of rewards and disappointments.

Why it matters: You’re not “wired” to want specific things. Your dopamine system responds to what you’ve learned predicts reward. This is why changing behaviour often requires creating new associations and breaking old ones—you’re literally retraining your brain’s prediction algorithm.

2. Current Physiological State: Dopamine Responds to Internal Needs

Dopamine doesn’t operate in a vacuum—your body’s immediate physiological state modulates it. This is where homeostatic regulation meets motivational drive.

Hunger is the perfect example. When your blood glucose drops, ghrelin (the “hunger hormone”) rises. Ghrelin doesn’t just make you feel hungry—it acts directly on dopamine neurons in the ventral tegmental area, increasing their firing rate and responsiveness to food-related cues. Dopamine then amplifies the motivational salience of food. Suddenly, that burger advert becomes irresistible. The smell of cooking triggers intense wanting. Your brain is screaming, “GO GET FOOD!”

But here’s the key: once you eat, and leptin (the satiety hormone) rises, dopamine responsiveness to food cues plummets. The same stimulus—a slice of cake—that triggered a dopamine surge when you were hungry now generates barely a blip when you’re full. The dopamine response is context-dependent, shaped by your body’s current needs.

This applies beyond hunger:

• Thirst modulates dopamine responses to water-related cues

• Sleep deprivation alters dopamine receptor availability, making you more impulsive and reward-seeking

• Pain or discomfort increases dopamine-driven motivation toward relief (painkillers, rest, comfort behaviours)

• Sexual arousal (driven by testosterone and estrogen) heightens dopamine responses to sexual cues

Your brain isn’t randomly motivated—it’s prioritising behaviours that address your most pressing physiological needs at any given moment. Dopamine is the amplifier that turns those needs into action.

Why it matters: This explains why the same person can crave different things at different times. You’re not weak-willed or inconsistent—your brain is responding to shifting internal states. Recognising this helps you design environments and strategies that work with your physiology, not against it.

3. Individual Differences in Receptor Sensitivity & Genetic Architecture

Not everyone’s dopamine system is built the same. Genetic variations in dopamine receptors, transporters, and enzymes create individual differences in the strength of people's motivation, reward, and impulse control.

Dopamine D2 Receptor Density: People with naturally lower D2 receptor availability tend to experience less reward signal from the same stimulus. To feel motivated or satisfied, they need more intense experiences. This predisposes them to:

• Sensation-seeking and risk-taking

• Substance use and addiction vulnerability

• Novelty-seeking behaviour

• Difficulty sustaining motivation for “boring” tasks

Conversely, those with higher D2 receptor density may be more sensitive to rewards and more easily satisfied by subtle pleasures—quiet accomplishment, intellectual engagement, routine habits.

Dopamine Transporter (DAT1) Variants: The DAT1 gene controls how quickly dopamine is cleared from the synaptic cleft. Variations here affect how long dopamine signals last and how intensely they’re experienced. Some variants are associated with ADHD, impulsivity, and risk-taking behaviour.

Catechol-O-Methyltransferase (COMT) Variants: This enzyme breaks down dopamine in the prefrontal cortex. The “warrior” variant (Val/Val) clears dopamine quickly—better for acute stress and rapid decision-making but worse for sustained focus. The “worrier” variant (Met/Met) clears dopamine slowly—better for complex problem-solving but worse under pressure.

Why it matters: Understanding that your dopamine baseline differs from others’ can be liberating. If you’re someone who needs more intense stimulation to feel motivated, that’s not a character flaw—it’s biology. You can design your life accordingly: seek out challenging goals, structure in novelty, use accountability systems. If you’re highly sensitive, you might thrive on routine, depth, and incremental progress.

4. Prefrontal Cortex Input: Goals, Values, and Identity

Your prefrontal cortex—the planning, decision-making, “who do I want to be” part of your brain—doesn’t just sit back and let subcortical dopamine systems run the show. It actively feeds information into the dopamine system about what should be important.

This is where top-down control meets bottom-up drive. Your conscious goals, values, and sense of identity shape which cues your dopamine system responds to.

If you’ve consciously decided that health is a priority and built an identity around being someone who takes care of their body, your prefrontal cortex tags fitness-related cues as important. When you see your gym bag or hear about a new workout, your dopamine system amplifies that signal—you feel motivated to go. You’re not relying on willpower alone; you’ve aligned your conscious goals with your unconscious motivational machinery.

This is why identity-based habits are so powerful. When you say “I am a runner” rather than “I want to run more,” you’re not just playing semantic games—you’re changing how your brain tags running-related cues. Your dopamine system starts treating them as self-relevant and important, generating motivation more automatically.

The flip side? When there’s a mismatch between your conscious goals and your learned associations or physiological drives, you experience that as “lack of willpower” or “self-sabotage.” Your prefrontal cortex wants one thing, but your dopamine system has learned to predict reward from something else. No amount of conscious effort can override that without retraining the system.

Why it matters: You can’t just “decide” to be motivated. But you can gradually reshape what your dopamine system responds to by:

• Consistently acting in line with your stated identity (even when unmotivated)

• Creating friction for unwanted behaviours (removing cues, increasing effort)

• Reinforcing desired behaviours with immediate small rewards (building new associations)

• Using implementation intentions (”When X happens, I’ll do Y”) to bypass conscious decision-making

Over time, your dopamine system learns the new patterns, and motivation becomes more automatic.

5. Environmental Cues & Availability: Context Is Everything

Dopamine is exquisitely sensitive to environmental triggers. A cue that’s been associated with reward—even tangentially—can trigger a dopamine surge and the urge to pursue that reward.

Walk past a bakery and smell fresh bread? If your brain has learned “bakery = delicious pastry = pleasure,” dopamine fires. You suddenly want a croissant even though you weren’t hungry 30 seconds ago. The cue triggered the prediction; dopamine created the wanting.

This is why recovering addicts are told to avoid places, people, and situations associated with their substance of choice. It’s not about “weakness”—it’s about context-dependent cue reactivity. When you’re in the environment where you used to drink or use drugs, your dopamine system fires in anticipation, creating powerful cravings. Remove the environmental cues, and the cravings often diminish dramatically.

The same principle applies to healthier behaviours. If you want to exercise more, put your gym clothes out the night before. That visual cue primes your dopamine system. If you're going to eat better, keep junk food out of the house—no cue, no dopamine spike, no urge.

Availability matters too. The easier a reward is to obtain, the stronger the dopamine-driven motivation. This is why your phone is so addictive: it’s always there, always available, always offering the possibility of reward (a new notification, an interesting post, a dopamine hit). Your brain learns that checking is low-effort, high-potential-payoff behaviour, so dopamine fires every time you see or think about your phone.

Why it matters: You can’t rely on motivation alone—you have to design your environment. Make desired behaviours easier (lower friction, add cues) and undesired behaviours harder (remove cues, increase friction). Your dopamine system will follow the path of least resistance toward whatever’s been most reliably rewarding in that context.

6. Other Neurotransmitter & Hormonal Systems: Dopamine Doesn’t Work Alone

Dopamine is potent, but it’s not operating in isolation. It’s constantly interacting with other neurotransmitters and hormones, and these interactions determine which dopamine-driven urges you act on and how you experience them.

Serotonin: Modulates mood, impulsivity, and risk assessment. Low serotonin increases impulsivity, making you more likely to act on dopamine-driven urges without considering consequences. High serotonin promotes behavioural inhibition and patience.

Testosterone: Increases dopamine receptor density and influences what feels rewarding—particularly status, competition, dominance, and sexual behaviour. Men with higher testosterone tend to be more motivated by competitive achievement and risk-taking. Testosterone also interacts with dopamine in the reward circuitry, making “winning” feel more satisfying.

Cortisol: Chronic challenges to homeostasis can sensitise dopamine pathways, particularly in the mesolimbic system, making comfort-seeking behaviours (food, alcohol, social media) feel more urgent and compelling. Cortisol also impairs prefrontal cortex function, reducing your ability to override impulses. This is why you crave junk food or doomscroll when stressed—your stress response hijacks your dopamine system.

Ghrelin and Leptin: As discussed earlier, these hunger hormones directly modulate dopamine neuron activity, shifting motivation toward or away from food depending on energy status.

Opioid and Endocannabinoid Systems: These determine the actual liking (pleasure) of rewards, which feeds back into future dopamine predictions. If something delivers less pleasure than expected, future dopamine responses to that cue diminish. If it provides more, they strengthen.

Why it matters: Your motivational state isn’t just about dopamine—it’s about the entire neurochemical environment. If you’re chronically stressed (high cortisol), sleep-deprived (disrupted dopamine receptor availability), or hormonally imbalanced (low testosterone, thyroid issues), your dopamine system won’t function optimally no matter how much you try to “hack” it. Address the whole system, not just one neurotransmitter.

The Bottom Line: Same Dopamine, Different Steering

So to answer Tom’s question directly: dopamine provides the motivational drive—the “go” signal—but it doesn’t determine what you’re motivated toward.

That’s determined by:

1. What your brain has learned predicts reward (associative conditioning)

2. Your current physiological needs (homeostatic signals)

3. Your genetic wiring (receptor density, transporter variants)

4. Your conscious goals and identity (prefrontal cortex input)

5. Environmental cues and availability (context-dependent triggers)

6. Your broader neurochemical state (other hormones and neurotransmitters)

One person is motivated toward biochemistry because their brain has learned that intellectual engagement predicts reward (curiosity satisfied, problem solved, status gained in their community). Their identity includes “someone who understands complex systems.” Their environment includes books, articles, and stimulating conversations. Their genetic makeup may favour cognitive depth over sensation-seeking. And their current state—perhaps well-fed, well-rested, low stress—supports sustained focus.

Another person is motivated toward a dram of whisky because their brain learned that alcohol predicts stress relief or social connection. Their environment includes cues (the bottle, the pub, the end of a workday). Their current state might involve high cortisol (stress), low serotonin (mood regulation issues), or unmet social needs. Their genetic profile might include variants that make them more impulsive or less sensitive to reward.

Same dopamine. Different learning. Different context. Different outcome.

This is why you can’t just “boost dopamine” and expect universal results. You can’t take a supplement, do a “dopamine fast,” or follow a one-size-fits-all protocol and expect it to solve motivation problems. You have to understand what your dopamine system has learned to respond to and deliberately reshape that over time through:

• Environment design (cues, friction, availability)

• Identity formation (who you want to be, not just what you want to do)

• Habit stacking (pairing new behaviours with established ones)

• Physiological optimisation (sleep, nutrition, stress management, hormonal health)

• Gradual reconditioning (consistently acting in line with new goals until your brain learns the new associations)

Your dopamine system is potent, but it’s also incredibly trainable. It responds to patterns. It learns from experience. And it can be guided—not by brute-force willpower, but by strategic environmental and behavioural design.

That’s the honest answer to Tom’s question. And it’s why understanding dopamine properly is so much more helpful than the “pleasure chemical” nonsense you’ll find in most articles.

References

1. Schultz W. Predictive Reward Signal of Dopamine Neurons. Journal of Neurophysiology. 1998;80(1):1-27.

2. Sharpe MJ, et al. Reward prediction error in learning-related behaviours. Frontiers in Neuroscience. 2023.

3. Watabe-Uchida M, Eshel N, Uchida N. Neural circuitry of reward prediction error. Annual Review of Neuroscience. 2017;40:373-394.

4. Kim HR, et al. Reward timescale controls the rate of behavioural and dopaminergic learning. eLife. 2023.

5. Hollerman JR, Schultz W. Dopamine Cells Respond to Predicted Events during Classical Conditioning. Journal of Neuroscience. 2005;25(26):6235-6242.

6. Bromberg-Martin ES, Matsumoto M, Hikosaka O. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron. 2010;68(5):815-834.

7. Dickson PE, et al. Mesolimbic dopamine ramps reflect environmental timescales. eLife. 2024.

8. Alhadeff AL, et al. Physiology, Obesity, Neurohormonal Appetite And Satiety Control. StatPearls [Internet]. 2024.

9. Ferrario CR, et al. Parallels and Overlap: The Integration of Homeostatic Signals by Mesolimbic Dopamine Neurons. Frontiers in Psychiatry. 2018.

10. Kenny PJ. Reward mechanisms in obesity: new insights and future directions. Neuron. 2011;69(4):664-679.

11. Stover PJ, et al. Neurobiology of eating behaviour, nutrition, and health. Journal of Internal Medicine. 2023.

12. Skibicka KP. The central GLP-1: implications for food and drug reward. Frontiers in Neuroscience. 2013;7:181.

13. Sun X, et al. Associations between ghrelin and leptin and neural food cue reactivity in healthy adults. NeuroImage. 2021.

14. Keramati M, Gutkin B. The interoceptive origin of reinforcement learning. Trends in Cognitive Sciences. 2025.

15. Augustine V, et al. Thirst recruits phasic dopamine signalling through subfornical organ neurons. Proceedings of the National Academy of Sciences. 2020;117(48):30744-30754.

16. Noble EP, et al. DRD2 dopamine receptor D2 gene. NCBI Gene Database. 2025.

17. Stelzel C, et al. Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity. Molecular Psychiatry. 2010;15:821-826.

18. Blum K, et al. SLC6A3 solute carrier family 6 member 3 (dopamine transporter). NCBI Gene Database. 2025.

19. Durazzo TC, Meyerhoff DJ, Nixon SJ. Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction. Drug and Alcohol Dependence. 2012;123:S59-S71.

20. Ponce G, et al. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse. Genes, Brain and Behavior. 2013;12(8):895-904.

21. Blum K, et al. Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome. Molecular Neurobiology. 2014;50:765-796.

22. Mata I, et al. DAT1 Polymorphism Is Associated with Risk Taking in the Balloon Analogue Risk Task (BART). PLoS One. 2012;7(6):e39135.

23. Arnsten AFT. The role of prefrontal cortex in cognitive control and executive function. Neuropsychopharmacology. 2022;47(1):72-89.

24. Rudebeck PH, et al. Controlling one’s world: identification of sub-regions of primate PFC underlying goal-directed behavior. Neuron. 2021;109(16):2485-2498.

25. Berkman ET. The Neuroscience of Goals and Behavior Change. Consulting Psychology Journal. 2018;70(1):28-44.

26. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction. Annual Review of Neuroscience. 2005;28:403-450.

27. Mohebi A, et al. Environmental context-dependent activation of dopamine neurons during Pavlovian conditioning. Nature Neuroscience. 2023;26:1022-1032.

28. Saunders BT, Robinson TE. The role of dopamine in the accumbens core in the expression of Pavlovian-conditioned responses. European Journal of Neuroscience. 2012;36(4):2521-2532.

29. Gentry RN, et al. Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts. Nature Communications. 2020;11:3764.

30. Nestler EJ. Addiction, Dopamine, and the Molecular Mechanisms of Memory. Neuron. 2000;25(3):515-532.

31. Cools R, et al. Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Comorbidity with other Clinical Disorders. Neuroscience & Biobehavioral Reviews. 2008;32(1):116-142.

32. Montoya ER, et al. Testosterone, cortisol, and serotonin are key regulators of social aggression. Frontiers in Behavioural Neuroscience. 2012;6:23.

33. Sandi C, Haller J. Stress and the social brain: behavioural effects and neurobiological mechanisms. Nature Reviews Neuroscience. 2015;16(5):290-304.

34. de Kloet ER, Joëls M, Holsboer F. Glucocorticoid regulation of diverse cognitive functions in normal and pathological conditions. Nature Reviews Neuroscience. 2005;6(6):463-475.

35. Lockwood PL, et al. Determinants and modulators of human social decisions. Trends in Cognitive Sciences. 2021;25(12):1025-1039.

---

Want to join the conversation? Comment below or join the discussion at Low-Carb Community on Skool.

Need personalised guidance? Book a consultation at The UK Carnivore.

Stephen Thomas BSc. Hons
www.theukcarnivore.com