There Really Is Something Strikingly Malicious in The Way Cocaine Rewards Our Brains : ScienceAlert

Scientists have identified the reward pathway which, when shared by drugs like cocaine and morphine, disrupts our natural desire to meet vital needs such as food and water.

This finding helps explain why addictive drug use may override the importance of eating and drinking, and could lead to new therapeutic interventions.

A New York team from Rockefeller University and the Icahn School of Medicine at Mount Sinai used mouse models to study responses to morphine and cocaine in reward brain circuits typically activated by hunger and thirsty.

“We have known for decades that natural rewards, like food and drugs, can activate the same region of the brain. But what we have just learned is that they impact the neuronal activity of surprisingly different ways,” says Jeffrey Friedman, a neuroscientist at Rockefeller University.

“A key takeaway is that addictive drugs have pathological effects on these neural pathways, distinct from, for example, the physiological response to eating a meal when hungry or drinking a glass of water when we are thirsty.”

We started the project by asking a simple question: How does the development of drug addiction interfere with our natural needs? This led us to collaborate across multiple areas to unravel the underlying mechanisms. I am truly grateful to work with these die-hard scientists! https://t.co/ffIX2ZHEHP

– Bowen Tan (@tbw_owl) April 19, 2024

The team used a whole-brain approach – mapping brain activity, imaging neurons in action in live mice, and sequencing the genetic activity of individual cells modified with CRISPR to see how cocaine and morphine might “hijack » their natural reward pathways.

They discovered that the brain’s nucleus accumbens (NAc) is more crucial than we thought, both for typical functions and for drug rewards. Neurons projecting to the NAc from the brain’s orbitofrontal cortex appear to be the culprits that reduce our desire for natural rewards when activated by drug use.

In conjunction with dopamine and serotonin, NAc uses motivation, positive reinforcement and pleasure to help us continue doing things that feel good.

“The NAc is a key node where underlying dopaminoceptive neurons direct and fine-tune animal behaviors toward their goals,” explains neuroscientist Bowen Tan, a graduate student at Rockefeller University during the study.

“What we haven’t been able to understand is how repeated exposure to drugs corrupts these neurons, leading to an escalation of drug-seeking behaviors and a shift away from healthy goals.”

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Cocaine – a central nervous system stimulant and one of the most addictive substances we know – has different effects on the brain than morphine, a pain-relieving opioid.

The researchers found that cocaine and morphine each activate a specific subset of neurons in the mouse NAc, most of which overlap with neurons that respond to natural rewards. But these overlapping neurons became more active when the mice were given cocaine or morphine than when they were given food or water.

Repeated exposure to the drugs gradually changed the mice’s behavior. They became more interested in cocaine and morphine, and less interested in regular food and water, which elicited the same baseline level of responding each time.

“By tracking these cells, we show that not only are similar cells activated across reward classes, but also that cocaine and morphine initially elicit stronger responses than food or water, and this amplifies with increasing exposure,” says neuroscientist Caleb Browne of the Icahn School. of medicine at Mount Sinai.

“After drug withdrawal, these same cells exhibit disorganized responses to natural rewards in ways that may resemble some of the negative affective states seen during withdrawal in substance use disorders.”

They also discovered a protein encoded by the Rheb gene that plays a critical role in interfering with typical neuronal communication, thereby changing the way the brain “remembers” rewards from food and water. The pathways associated with this particular protein could constitute a therapeutic target.

Understanding how addictive drugs can disrupt a very well-coordinated system that normally links physiological needs to appetite-related behavior could mean we find better ways to manage addiction, for which there are currently few effective treatments.

“Ongoing research will aim to define how multimodal information flow is incorporated into value calculations in brain cells and how this crucial mechanism allows drugs to override the processing of natural rewards, leading to addiction.” , explains Eric Nestler, neuroscientist at Mount Sinai.

The research was published in Science.