Latest developments in causes and treatments



New Research Into How Addiction Impacts the Brain’s Reward Pathway

We’ve been writing quite a bit about addiction and the brain lately at AddictionNews. Last week, we reported on cue-sensitivity and how it impacted EEGs of obese adults. We also looked at what the National Institute on Drug Abuse says about addiction and the brain. We followed that up with a post, yesterday, on using low-intensity focused ultrasound to treat substance use disorders. Today, we’re taking a look at studies of the brain’s reward system.

We’ll start with breaking news out of Rockefeller University in New York that scientists there working together with researchers at Mount Sinai have identified a “common reward pathway” in the brain. “One of the big takeaways here,” said Jeffrey F. Friedman, M.D., Ph.D., who runs a molecular genetics lab at Rockefeller University’s Howard Hughes Medical Center, “is that addictive drugs have pathologic effects on these neural pathways…”

The objective of Dr. Friedman’s research was to more clearly identify how the process of addiction transpires in comparison to the natural reward pathways for thirst and hunger that motivate people to drink and eat. In a research article for Science, the authors’ abstract states:

Decades of research [have] shown that brain systems processing natural rewards are also impacted by drugs of abuse at the physiological, circuit, cellular, and molecular levels.

In studies on mice, the researchers say, “[W]e identify the nucleus accumbens (NAc) as a central hub necessary for both cocaine and morphine to disrupt natural reward (food and water) consumption.” Repeated exposure to drugs of abuse resulted in an escalation of drug response, followed by a degradation of the natural reward system upon withdrawal of the drugs of abuse. The scientists describe the “essential role” of the protein RHEB (Ras Homolog Enriched in Brain) in “diminishing natural reward consumption after chronic exposure to drugs of abuse.”

The authors conclude that their research reveals that: 

[A] mechanism enabling drugs of abuse to commandeer natural reward processing systems. Repeated drug exposure progressively augments the activity of natural reward-responsive nucleus accumbens (NAc) ensembles, interfering with homeostatic need fulfillment mediated by means of RHEB.

Many other researchers are exploring the role of the nucleus accumbens (NAc) in addiction. In a survey article, a team of researchers from the medical faculty at the University of Gdansk teamed up with the Polish Institute of Health Sciences to “combine the results of morphological studies with molecular, genetic, and behavioral data” concerning the function of NAc and its role in the brain’s reward system.

The authors demonstrate that the “integrative role” of NAc requires cooperation among several neurotransmitter systems and receptors that “modulate synaptic plasticity” and determine the effects of drugs on behavioral responses. They go on to elaborate on each of these systems, including dopamine, glutamine, GABA, serotonin, and noradrenaline. 

As to the effects of addiction on the NAc, the authors share fascinating research on nicotine, showing that it affects neural development even in the womb, altering the expression of certain genes. Exposure to nicotine during adolescence “reduces cognitive abilities and diminishes attentional performance,” the authors say. In a key paragraph on stress and the brain, the authors state:

Some evidence indicates that early-life adversity experiences like poverty, chaotic environment, maternal separation or poor parental care may significantly contribute to dysfunction of the brain’s reward system. They may lie at the base of the affective disorders, such as depression and anhedonia at the later stages of development. Moreover, they also make those in that stage prone to the development of addiction.

Which takes us all the way back to what comes first, the chicken or the egg, the stress or the addiction? If stress is leading to addiction, then moderating stress should be a logical treatment for moderating addiction. Where does the stress come from? 

This leads us to displacement: a build-up of brain energy resulting from a stressful situation that is displaced through eating, drinking, taking drugs, and other compulsive behaviors including gambling, gaming, shopping, sex addiction, and even work addiction. Displacement may be the most common, least understood, element in the brain’s reward system and the key to understanding the origins of addiction. We’ll have more to say about displacement in the coming weeks.

Written by Steve O’Keefe. First published April 30, 2024.


“Newly discovered brain pathway sheds light on addiction,” Rockefeller University Science News, April 18, 2024.

“Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need,” Science, April 19, 2024.

“Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System,” International Journal of Molecular Science, September 2021.

Image Copyright: Kenneth C. Zirkel, used under Creative Commons license.


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