Too Much (or too little) Dopamine Killed Pavlov’s Dogs
Our friend would always microdose on her amphetamines to help her cope with her ADD. He’d ask for the leftovers and take it with some Xanax or Valium to experiment and observe if its effects contradict each other. Apparently, he’s an ‘expert’ at mixing different kinds of drugs. He said he tried all forms of stimulants and depressants: drugs, alcohol, sex, and I’m pretty sure he tried self-flagellation. He said he liked doing this so he can test which substances or activities would give him his desired effects for his brain. Unfortunately, when you’re at your low and tripping, you can’t control what your unconscious and emotions feed you. Take high doses of the over-the-counters and you might grow dependent on them. But he insisted that he wasn’t stupid and that he knew what he was doing. So I let him be but warned him that if he continues his quest searching for instant pain and pleasure, he soon might OD.
Degeneration, debilitation, defiance, dejection, deprivation, destitution, depression, disgruntlement, disruptiveness, delusions, desires, drugs, dystopia, dysfunctional, demonic, dangerous... among my collection of favorite words starting with the letter 'd,' dopamine holds a significant place. This hormone, this neurotransmitter, plays a crucial role in our experience of pleasurable thrills. However, like many other things in life, an excess or deficiency of dopamine can have detrimental effects.
The origins of the dopamine system trace back to a time before animals diverged from fungi. Some studies suggest that the last common ancestor of eukaryotes acquired genes responsible for dopamine synthesis, and the production of messenger molecules, through horizontal gene transfer from bacteria (for more information on HGT, refer to "Rosetta and the Transients"). The presence of dopamine-like genes in animals facilitated communication between cells. Over time, through both horizontal gene transfer and vertical gene transfer from parent to offspring, cell-to-cell interaction in the nervous, neuroendocrine, and immune systems of animals became possible.
Dopamine plays a critical role in facilitating neuronal signaling and communication within the brain. Neurons communicate with each other in specialized spaces called synaptic clefts, where they pass chemical signals. When the presynaptic neuron is excited by electrical signals (action potentials), neurotransmitters like dopamine are released into the synaptic cleft. Dopamine then interacts with the receptors of the postsynaptic neuron, triggering its response. Some dopamine diffuses out of the cell, while the remainder is reabsorbed or recycled by the presynaptic neuron for future use.
Various dopamine pathways in the brain are associated with functions such as motor control, hormonal regulation, and reward-motivated behaviors in humans. Dopamine plays a major role in our ability to experience pleasure from food, drugs, sex, and even pain. It has been a key ingredient in the development of our reward system, providing us with evolutionary and adaptive benefits, such as learning, goal-oriented behavior, and sensitivity to social cues and cooperation. The primary function of our reward system is to provide our bodies with substances necessary for maintaining cellular functions and regulating homeostatic balance. When our body's balance is disrupted (e.g., hunger or thirst), we seek out the substances that can fulfill our needs and support our survival. We eat when we're hungry, drink when we're thirsty, and create to fill the void.
As we anticipate rewarding stimuli, dopamine levels in our brains increase, motivating us to make intense efforts to obtain these pleasurable rewards. Similar to Pavlov's dogs salivating at the sound of a bell, we respond with excitement to rewarding stimuli. Excessive exposure to rewarding stimuli can overwhelm the brain's reward system, flooding it with excess dopamine. Prolonged or chronic intake of rewarding stimuli can lead to a reduction in dopamine receptors in the brain, making us more susceptible to cravings and addictive behaviors. In cases where dopamine levels are extremely depleted, homeostasis may succumb to stimuli that cause more harm than benefit to our bodies. Our vulnerability to indulge in harmful stimuli, such as overeating, substance abuse, self-inflicted pain, or excessive sexual activity, is influenced by a combination of genetic factors and our environment, including epigenetics. Some individuals may be more predisposed to addictive behaviors due to genetic variations (polymorphisms) in dopaminergic and other neurotransmitter-related genes.
Exposure to extreme stress or trauma, such as coming from an abusive family, can increase our vulnerability to a dysfunctional dopamine system. A dysfunctional dopamine system has been associated with various conditions and disorders, including Parkinson's disease, attention deficit disorder (ADD), dementia, schizophrenia, mood disorders, and addiction. These conditions often manifest through behavioral and learning problems, such as impulsivity, compulsivity, inattention, oppositional behavior, low self-esteem, mood swings, sleep disturbances, anxiety attacks, explosive outbursts, reactive attachment issues, and substance abuse problems. It's important to recognize that these "disorders" are social constructs, and they can significantly impact specific brain regions and impede their normal development. Mismanagement of these symptoms can have cascading effects that permanently alter and damage the functioning of our minds and bodies.
When our brains and bodies are in desperate need of assistance, they tend to switch from manual control to automatic mode, making us more susceptible to suggestion. Our primal instincts take over, and like a person possessed, our brains may yield to powerful stimulants and intoxicants that are erroneously perceived as "useful" or "corrective." We seek shortcuts in life, pursuing short-term pleasures. We indulge excessively in food, drugs, sex, pain, social media, or any activities that provide a temporary euphoria in an attempt to alleviate and distract ourselves from our responsibilities. As we continually give in to these addictive behaviors and drives, we push our bodies beyond their limits. We push ourselves toward self-destruction, compromising our quality of life and succumbing to an untimely fate - death.
Unfortunately, some individuals mistakenly view "quick fixes" and hedonism as gateways to freedom. However, our ability to control our impulses holds far greater power than succumbing to short-term distractions. By hacking into our dopamine system and establishing long-term goals for ourselves, we can ensure a steady supply of dopamine without resorting to excessive indulgence in false happiness or being consumed by melancholy. Building a balanced and fulfilling life requires cultivating the capacity to regulate our impulses and seek meaningful and sustainable sources of happiness and fulfillment.
References/ Further readings:
Carondinaud, B., Gilbert, J. M., Liu, F., Sugamori, K. S., Vincent, J. D., Niznik, H. B., & Vernier, P. (1997). Evolution and origin of the diversity of dopamine receptors in vertebrates. In Advances in Pharmacology (Vol. 42, pp. 936-940). Academic Press.
Bain, D., & Brady, M. (2014). Pain, pleasure, and unpleasure. Review of philosophy and psychology, 5(1), 1-14.
Blum, K., Gondré-Lewis, M., Steinberg, B., Elman, I., Baron, D., Modestino, E. J., ... & Gold, M. S. (2018). Our evolved unique pleasure circuit makes humans different from apes: Reconsideration of data derived from animal studies. Journal of systems and integrative neuroscience, 4(1).
Darvas, M., Wunsch, A. M., Gibbs, J. T., & Palmiter, R. D. (2014). Dopamine dependency for acquisition and performance of Pavlovian conditioned response. Proceedings of the National Academy of Sciences, 111(7), 2764-2769.
Dreher, J. C., Kohn, P., Kolachana, B., Weinberger, D. R., & Berman, K. F. (2009). Variation in dopamine genes influences responsivity of the human reward system. Proceedings of the National Academy of Sciences, 106(2), 617-622.
Engel, G. L. (1962). Anxiety and depression-withdrawal: The primary affects of unpleasure. International Journal of Psycho-Analysis, 43, 89-97.
Iyer, L. M., Aravind, L., Coon, S. L., Klein, D. C., & Koonin, E. V. (2004). Evolution of cell–cell signaling in animals: did late horizontal gene transfer from bacteria have a role?. TRENDS in Genetics, 20(7), 292-299.
Kooij, S. J., Bejerot, S., Blackwell, A., Caci, H., Casas-Brugué, M., Carpentier, P. J., ... & Gaillac, V. (2010). European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD. BMC psychiatry, 10(1), 67.
Niznik, H. B., & Van Tol, H. H. (1992). Dopamine receptor genes: new tools for molecular psychiatry. Journal of psychiatry and neuroscience, 17(4), 158.
Pascoli, V., Terrier, J., Hiver, A., & Lüscher, C. (2015). Sufficiency of mesolimbic dopamine neuron stimulation for the progression to addiction. Neuron, 88(5), 1054-1066.
Pavlov, P. I. (2010). Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Annals of neurosciences, 17(3), 136.
Pavlov, I. P. (1962). Psychopathology and psychiatry. Transaction Publishers.
Rho, J. M., & Storey, T. W. (2001). Molecular ontogeny of major neurotransmitter receptor systems in the mammalian central nervous system: norepinephrine, dopamine, serotonin, acetylcholine, and glycine. Journal of child neurology, 16(4), 271-280.
Saunders, B. T., Richard, J. M., Margolis, E. B., & Janak, P. H. (2018). Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties. Nature neuroscience, 21(8), 1072-1083.
Singh, I. (2008). Beyond polemics: science and ethics of ADHD. Nature Reviews Neuroscience, 9(12), 957-964.
Sousa, A. M., Zhu, Y., Raghanti, M. A., Kitchen, R. R., Onorati, M., Tebbenkamp, A. T., ... & Liu, F. (2017). Molecular and cellular reorganization of neural circuits in the human lineage. Science, 358(6366), 1027-1032.
Squire, L., Berg, D., Bloom, F. E., Du Lac, S., Ghosh, A., & Spitzer, N. C. (Eds.). (2012). Fundamental neuroscience. Academic Press.
Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Telang, F. (2011). Addiction: beyond dopamine reward circuitry. Proceedings of the National Academy of Sciences, 108(37), 15037-15042.
Wassum, K. M., Ostlund, S. B., Balleine, B. W., & Maidment, N. T. (2011). Differential dependence of Pavlovian incentive motivation and instrumental incentive learning processes on dopamine signaling. Learning & memory, 18(7), 475-483.
Yamamoto, K., & Vernier, P. (2011). The evolution of dopamine systems in chordates. Frontiers in neuroanatomy, 5, 21.