Hair's-breadth separates pleasurable reward from fearful dread

Dopamine's opposing effects separated by a few millimeters in the brain

The neurotransmitter dopamine induces both desire and dread, according to new animal research published in the July 9 issue of The Journal of Neuroscience.

Although dopamine is well known to motivate animals and people to seek positive rewards, the study indicates that it also can promote negative feelings like fear. The finding may help explain why dopamine dysfunction is implicated not only in drug addiction, which involves excessive desire, but in schizophrenia and some phobias, which involve excessive fear.

"This study changes our thinking about what dopamine does," said Howard Fields, MD, PhD, of the University of California, San Francisco, an expert unaffiliated with the study. "There is a huge body of evidence out there to support the idea that dopamine mediates positive effects, like reward, happiness, and pleasure. This study says, it does do that, but it can also promote negative behaviors through actions in an adjacent brain area," Fields said.

Kent Berridge, PhD, and his colleagues at the University of Michigan, identified dopamine's dual effect on the nucleus accumbens, a brain region that motivates people and animals to seek out pleasurable rewards like food, sex, or drugs, but is also involved in fear. They found that inhibiting dopamine's normal function prevented the nucleus accumbens neurons from inducing both rewarding and fearful behaviors, suggesting that dopamine is important in both.

In previous research, Berridge and colleagues showed that a distance of only a few millimeters separated desire and dread functions in the nucleus accumbens (which is only about 5 millimeters long in humans). Because dopamine is an important neurotransmitter in this brain structure, the researchers investigated its role in generating these functions in the current study.

When dopamine was allowed to act normally, injection of a chemical to model normal signaling in the front of the nucleus accumbens caused rats to eat nearly three times as much as they normally do. In contrast, injection of the chemical in the back of the nucleus accumbens caused rats to display fearful behavior normally shown in response to a predator.

"It has always been assumed that discrete neurotransmitters might separate fear from desire, but this report shows that transmitters such as dopamine play a constant role and that the anatomy is providing for emotional discretion," said Peter Kalivas, PhD, at the Medical University of South Carolina, who was unaffiliated with the study.

Berridge speculates that disruption of dopamine neurotransmission in one region of the nucleus accumbens may be a mechanism for pathological excesses of fear in disorders such as schizophrenia, whereas disruptions in dopamine neurotransmission in an adjacent region may be a mechanism for excessive reward-seeking in conditions like addiction.

The research was supported by the National Institute of Mental Health and the National Institute on Drug Abuse.

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Faure A, Reynolds S, Richard JM, Berridge KC. Mesolimbic Dopamine in Desire and Dread: Enabling Motivation to Be Generated by Localized Glutamate Disruptions in Nucleus Accumbens. J. Neurosci. 2008 28: 7184-7192   [Abstract]