True behavior of the `pleasure molecule' will reshape how we treat
psychiatric diseases and addiction

Date:
September 16, 2021
Source:
Vanderbilt University
Summary:
Discovery shows that dopamine is not a reward molecule at all,
calling for revision of textbook facts regarding the hormone's
role in the brain.



FULL STORY ========================================================================== Pioneering research shows that dopamine levels increase in response to stressful stimuli, and not just pleasurable ones, potentially rewriting
facts about the "feel-good" hormone -- a critical mediator of many
psychiatric diseases. This discovery is cause to rethink treatment for psychiatric disease and addiction.


==========================================================================
This research was led by Erin Calipari, assistant professor of
pharmacology, and Munir Gunes Kutlu, a postdoctoral fellow in Calipari's laboratory.

"In the press, dopamine is often referred to as a 'pleasure molecule' or
a 'reward molecule,'" said Calipari, who also is a faculty member of the Vanderbilt Brain Institute and the Center for Addiction Research. "In the scientific community, research has helped us understand that dopamine's
role in learning and memory is more complex than that, but we did not have
a complete and accurate theory that could explain what dopamine actually
does in the brain." The prevailing model, called the reward prediction
error theory, is based on the idea that dopamine signals predictions about
when rewards will occur. This theory suggests that dopamine is a tracker
of every error we make when we try to achieve rewards. The authors show
that RPE is only accurate in a subset of learning scenarios by proving
that "while rewards increase dopamine, so do stressful stimuli," Calipari
said. "We then go on to show that dopamine is not a reward molecule at
all. It instead helps encode information about all types of important and relevant events and drive adaptive behavior -- regardless of whether it
is positive or negative." The researchers collaborated with Lin Tian, professor and vice chair of biochemistry and molecular medicine at UC
Davis, to use cutting-edge technology to study an unprecedented diversity
of neurobehavioral processes related to dopamine release. The authors
used machine learning and computational modeling to analyze the data,
along with optogenetic manipulations, which use light to control activity
of genetically modified neurons.

The analysis established a novel computational model of behavior that
shows "accurate prediction of the behavioral impact of optogenetic perturbations of dopamine release." Calipari concluded that "this work
replaces our current understanding with a formalized theory and calls
for revision of textbook facts regarding dopamine in the central nervous system." Why It Matters


==========================================================================
"A common theme of all drugs of abuse is that they increase dopamine
release in the brain, which helped feed the notion of dopamine as a
reward molecule. This work clearly demonstrates a much more sophisticated
role for this neurotransmitter, and it means we need to rethink models
of addiction that depend on the dopamine/drug reward mentality," said
Danny Winder, director of the Vanderbilt Center for Addiction Research.

Calipari emphasizes that "these data rewrite facts about dopamine,
including what it encodes within the brain and how it drives
behavior." This is incredibly important as dopamine is dysregulated in Parkinson's disease and in nearly every psychiatric disease: addiction,
anxiety and depression, schizophrenia and others, she said. Understanding
what these dopamine deficits mean will be critical in understanding
patients' symptoms and in developing better evidence-based treatments
for these diseases.

What's Next? "We plan to research how this framework fits into our understanding of drug addiction and how drugs alter dopamine signaling
to disrupt behavior within this novel framework," Calipari said. "Most
of our understanding of addiction neurobiology centers around dopamine
and the dopaminergic network, as many therapeutic approaches that aim
to treat addiction target dopamine. However, altering dopamine without
having a full understanding of what dopamine actually does may lead to
many unforeseen side effects, and more importantly, failed treatment strategies. This new knowledge about what dopamine actually does will
affect many fields outside neuroscience and have a strong impact on
human lives and health outcomes." Funding This work was supported by
National Institutes of Health grants DA048931, DA042111, KL2TR002245,
GM07628 and DA045103, as well as by funds from the Vanderbilt University Medical Center Faculty Research Scholar Award, the Pfeil Foundation,
the Brain and Behavior Research Foundation, the Whitehall Foundation
and the Edward Mallinckrodt, Jr. Foundation.

========================================================================== Story Source: Materials provided by Vanderbilt_University. Original
written by Aaron Conley.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Munir Gunes Kutlu, Jennifer E. Zachry, Patrick R. Melugin,
Stephanie A.

Cajigas, Maxime F. Chevee, Shannon J. Kelley, Banu Kutlu, Lin Tian,
Cody A. Siciliano, Erin S. Calipari. Dopamine release in the nucleus
accumbens core signals perceived saliency. Current Biology, 2021;
DOI: 10.1016/ j.cub.2021.08.052 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210916131312.htm

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