Location matters

Dopamine conducts a frenzied song of craving at one end of a tiny brain region and a panic-stricken hymn at the other. Depending on where along the length of the region the neurotransmitter is triggered, it elicits emotions ranging from desire to disgust, a new study shows.

“The roles [of dopamine] may be partitioned, and perhaps defined, by anatomy,” comments Emily Hueske, a neuroscientist at the Massachusetts Institute of Technology.

With the recent study, researchers have come one step closer to explaining how dopamine performs a spectrum of functions. Dopamine interacts with spatially coded signals so that its output varies from one end of a brain region to the other, the team reports in the July 9 Journal of Neuroscience.

In the long-term, drugs might be developed to locally treat various dopamine-mediated disorders such as drug addiction, obsession, obesity and anxiety.

Kent Berridge, a neuroscientist and psychologist at the University of Michigan in Ann Arbor, and his colleagues set out to understand how dopamine could lead to desire for a reward, and then turn around and cause fear, pain and stress.

Berridge’s team focused on the area of the nucleus accumbens known as the pleasure center in all mammals. The researchers report the effects of tampering with dopamine and another chemical messenger, the glutamate neurotransmitter, along the length of the nucleus accumbens of rats.

A tiny, localized injection at the front end disrupted glutamate and turned normal rats into binge-eaters. But when researchers injected the same glutamate blocker at the back end of the nucleus accumbens, the rats stopped eating and became fearful — kicking up sand at the bottom of their cages, as wild rodents are wont to do when a snake or a scorpion is in their midst, Berridge says.

When both dopamine and glutamate were blocked, the rats did not display the extreme behaviors. In nature, the interaction between the two may guide how a rat responds to signals from the environment. Glutamate may bring in information from the outside world, and dopamine may act on that information, Berridge suggests.

Because the injections only blocked glutamate or dopamine in tiny bits of the nucleus accumbens, the researchers were able to map out a millimeter-by-millimeter gradient of reactions over the region. “The brain cares where you are exactly,” Berridge says.

“This is perhaps a surprise,” says behavioral neuroscientist Richard Palmiter of the University of Washington in Seattle. He’s not shocked about the gradient of dopamine-mediated reactions because desire and dread aren’t completely unrelated. Regardless of how the rat responds to a stimulus, “dopamine is basically saying: ‘Hey, pay attention to your environment’,” he says.

Still, this study shows how motivation for a reward can turn to fear within a single structure, Berridge says.

The researchers describe the gradient as a keyboard, with keys going from desire to fear. The minute keyboard gradient found in the rats may translate into a slightly larger, centimeter-by-centimeter keyboard in humans’ nucleus accumbens. Berridge speculates that the boundaries of “keys” are skewed in people with certain disorders, such that a sensation produces more pleasure than it should in an addict or too much fear in schizophrenic patients.

Once scientists know what underlies the front-to-back gradient, drugs could be refined to more accurately treat separate disorders, says Charlotte Boettiger, a behavioral neuroscientist at the University of North Carolina at Chapel Hill. It may be years before those treatments are developed, however. “We don’t presently have a way to target drugs to one part or the other.”

A Squirrel in Distress:

FEAR FACTOR from Science News on Vimeo.

In this video, a squirrel defensively kicks up sand when it spots a rattlesnake. Other rodents instinctively kick in the face of fear. In the lab, rats kicked up their cage bedding when researchers tampered with certain brain chemicals. Video courtesy of BBC & National Geographic, provided to Kent Berridge by Profs. D.H. Owings & R.G. Coss