Everyday choices are driven by the pursuit of rewards: from savoring delicious meals and enjoying refreshing drinks, to intimate relationships and caring for loved ones. While many of these behaviors are crucial for survival, the relentless chase for rewards can sometimes turn perilous.

Our memories of rewards shape our decisions and existence. Positive experiences linked to these memories guide our preferences and choices. For instance, a sugary dessert that brings joy can reinforce the habit of indulging in sweets, while a delightful dinner at a favorite restaurant keeps us coming back for more.

A deeper understanding of how these reward memories function can be pivotal in treating addictions, which often stem from an obsession with harmful substances. Striking a balance is essential; entirely eliminating the pursuit of rewards could hinder vital behaviors like eating and reproduction. However, specifically targeting the memories associated with drug use might hold the key to reducing addiction.

As a behavioral neuroscientist focused on addiction, my team is examining how the brain forms and processes reward memories. We differentiate between natural rewards—like food, water, and sex—and those from drugs such as fentanyl and cocaine, paving the way for more effective addiction treatments.

What Exactly Is Memory?

To unravel the mysteries of reward memories, it's crucial to grasp the neurobiology of memory. The term 'engram' was coined by zoologist Richard Semon in 1904, describing the brain’s physical representation of memories. Psychologist Donald Hebb proposed that interconnected brain cells firing simultaneously create the framework for memory.

Recent advancements in neuroscience have affirmed that these 'neuronal ensembles'—groups of brain cells activated together—are likely the very foundation of memory. Although the full process of how these memory ensembles are formed remains unclear, the flexibility of neurons appears pivotal.

Now, researchers can create artificial memories and manipulate the emotional weight of existing ones in laboratory settings, primarily using animal models. Techniques such as activating certain neuronal groups can lead to the formation of false memories, as witnessed in experiments using genetically modified mice.

Tackling Substance Use Disorders

Neuronal ensembles present untapped potential in addressing substance use and other reward-related disorders, including gambling, eating disorders, and depression. Natural rewards generate pleasurable sensations that reinforce the behaviors that lead to them, a concept known as positive reinforcement.

However, drug use complicates this dynamic. For instance, cocaine produces an exhilarating high followed by an irritable crash. This cycle often encourages further drug use while undermining essential survival behaviors like eating and socializing.

Understanding how drug-related memories operate within neuronal ensembles might illuminate the path to effective treatments for addiction, particularly in light of many individuals misusing multiple substances simultaneously. By tagging neurons active during drug-seeking behaviors in modified mice, my team is mapping how these reward memories interplay when subjects are exposed to various substances, including common combinations like cocaine and fentanyl.

Decoding the Brain’s Addiction Pathways

The challenge lies in unraveling how drugs alter the brain's natural reward mechanisms. Since the brain’s processing centers for natural and drug-related rewards largely overlap, creating targeted treatments is a complex endeavor. However, understanding how different drugs affect genes and neuronal circuits may lead to innovative approaches to treat addiction without disrupting vital natural reward-seeking behaviors.

We are even utilizing fruit fly models to delve into the genetic activity of neuronal ensembles related to cocaine-seeking behavior, identifying genes that could serve as targets for reducing aberrant reward memory activity.

The Promise of Psychedelics in Addiction Recovery

Substance abuse often creates harmful neural pathways reinforced by intrusive thoughts and repetitive behaviors. Surprisingly, psychedelics could hold the potential to reset these pathways by providing a 'system reboot' for the brain.

Emerging clinical trials suggest that psychedelics might aid in treating addictions to tobacco, alcohol, and opioids, with early evidence showing increased periods of abstinence and diminished cravings.

Our lab is currently exploring how psilocin, a key compound in psilocybin, impacts drug-related memories in mice. We aim to uncover whether psilocin can modify fentanyl-seeking behavior and determine what type of memory it establishes in the brain, potentially altering the influence of prior cocaine memories.

In essence, while reward memories play a pivotal role in survival, they can also pave the way to addiction. By exploring the cellular and genetic mechanisms behind how the brain processes rewards, we may be able to craft more effective treatments for addiction, preserving the essential reward-seeking behaviors necessary for life.