Fixing the leak: An opioid treatment for dopamine disorders?

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Dopamine, a small molecule derived from the amino acid tyrosine, plays a significant role in regulating multiple essential brain functions, including movement, mood, and motivation, as well as multiple cognitive functions, including attention and memory. Dopamine signaling in the brain is a complex process, with many mechanisms in place to accelerate or slow down dopamine’s effects. When dopamine is released from nerve cells, its efficient removal to limit signaling occurs through the activity of special proteins called “transporters,” ensuring a shorter action of dopamine in the brain.

Disruptions in dopamine signaling have been linked to several neuropsychiatric disorders, including ADHD, schizophrenia, bipolar disorder, autism spectrum disorder, substance use disorder, and addiction. Current treatments for dopamine-related conditions use agents that can either block or enhance dopamine signaling, such as stimulants used to treat attention-deficit/hyperactivity disorder, including amphetamines, which can have unwanted side effects or lead to addiction. The power of dopamine to regulate brain mechanisms of thought, mood, and reward has kept scientists searching for better ways to control its actions.

In a newly published study in the journal Molecular Psychiatry, researchers from Florida Atlantic University and their collaborators have discovered a potentially safer yet effective treatment for multiple disorders that display altered dopamine signaling. The “key?” A molecule that targets a specific protein called the kappa opioid receptor (KOR).

Opioids are commonly known as powerful painkillers with strong psychoactive effects. They increase dopamine signaling in the brain, producing pleasurable sensations that can encourage repeated use and, over time, lead to addiction. Both endogenous and illicit opioid molecules act on signaling proteins termed receptors. But all opioid receptors are not the same.

In the current study, the researchers targeted KOR, a subtype of opioid receptor that, when activated, can decrease synaptic dopamine levels by decreasing dopamine release and increasing the availability of synaptic dopamine transporters, thereby halting the dopamine signal. Instead of activating KOR, scientists used a drug that can block it. But wouldn’t this cause addiction by elevating dopamine?

Source: News Release
Florida Atlantic University
May 30, 2025