Ancient systems in the brain drive human cravings

Neuroscience is the new black, when it comes to fashion in scientific research.

"The gene was the central issue in biology in 20th century," Nobel Laureate Dr. Eric Kandel, neuroscientist at Columbia University said in an interview in Toronto recently. "The mind is the essential issue for biology in the 21st century."

"And certainly if you think of public health consequences, the diseases, pain, schizophrenia, depression, manic depressive disorder, post traumatic stress disorder, God knows what, so many miseries of humankind come from psychiatric and neurological disorders," Kandel added.

Back in the 1960's, when Kandel began his Nobel prize winning work searching for the biological source of memory, neuroscience was a lonely field. "It didn't interest many biologists. Anatomy was considered boring, and electrophysiology was too technically complicated for most scientists to pay attention to," he said.

Richard Beninger is a behavioral neuroscientist at Queen's University, who recalls that as a student he studied the brain as a collection of parts. "You could see white matter and dark matter and lots of fine detail, right down to the neuron level, but it was all morphology, structure," he said.

"But all of that changed, once scientists began to understand the chemical pathways in the brain. The morphology is still there, but now we know what the transmitter systems are. So we have a whole new brain only in the last 40 years to work with," Beninger said.

The mind is the essential issue for biology in the 21st century, says Nobel Laureate Dr. Eric Kandel. (Lucas Jackson/Reuters)

Today's technology allows scientists to put living, breathing humans into an magnetic resonance imaging machine, tell them to think about something, and watch as the biological traces of thought appear and disappear in colorful bursts, measured by changes in blood oxygen levels. It means scientists can now explore the neural landscape in real time, and chart the cognitive forces that have shaped our species from our earliest days.

As they investigate this neural wonderland, scientists are probing the very essence of what makes us human. It's as though they are lifting the hood of humanity, and tinkering with the wiring to find how what makes us do what we do. And they are discovering that the secret to everything we do, think, or feel, is in that wiring, a constantly changing network of neuronal connections sculpted by evolution and fired by electrical and chemical interactions.

Dr. Kandel calls it the most complex organizational structure in the universe. "So we're far from understanding it completely, very far, but the beginning has been quite dramatic," he says.

"It's certainly extraordinary, our entire experience of life, all of our mental experiences, if they all result from the activity of chemistry in our brain, the activity of neurotransmitters and neurocircuits, it's amazing," Beninger said.

Dopamine key to behaviour

For Richard Beninger, dopamine is the most fascinating neurotransmitter, allowing us to interact with our environment, sending us in search of the things we need for survival. "Something that's biologically valuable, food, for example, water, sexual partner, social companion, social cooperation, those are things that activate the dopamine system," he says.

"These systems are ancient, you know, fruit flies have similar systems, and worms," he says. "They're found in fish and all vertebrates, they're very old, these dopamine neurons," Beninger said.

Which means the same chemical impulses that lead a fruit fly to dive into your wineglass also makes you reach for the bottle and pour that second glass.

"When dopamine neurons are activated, whatever's being encountered at the time gets a stronger ability to attract in the future," Beninger says. "So for an animal in the wild, food-related stimuli, things that signal food, like a particular place, a particular object, then acquire the ability to draw the animal in the future."

Dopamine does its work through a form of unconscious learning, teaching the brain to recognize environmental cues, sights sounds, smells, feelings that lead back to the thing that first excited the reward pathway, even if that 'thing' is dangerous. "So drugs that are abused by people, all of them activate the dopamine system," Beninger explains.

The brain and food addiction

Increasingly scientists also believe food can hijack the brain's reward system. At York University, Professor Caroline Davis is studying the biological basis of food addiction. She says the brain's reward system can be particularly sensitive to highly processed food with combinations of salt, sugar, fat and flavours found nowhere in nature.

"Because they're so palatable, we tend to eat a lot of them and they give us a greater dopamine boost than broccoli does," Davis said. "The things loaded with sugar, loaded with fat, salt, in combination they're very, very hard to resist and there's evidence that if you eat enough of these foods, in some vulnerable people, they display behavior that is very similar to the behavior that we see in other addicts."

When lab rats are given access to sugary food, they binge, and when the sugar is taken away they show physical withdrawal systems that resemble the animal's withdrawal from heroin. Research has shown that dopamine is one of the pathways activated in these sugar-addicted mice.

Caroline Davis has discovered a dopamine link in food-addicted humans, a genetic profile that is associated with stronger dopamine signalling, and she believes those genes might make some people more vulnerable to dopamine's cues.

"People that tend to be very sensitive to reward, our data suggests, it may be more difficult for them, in this environment. In another era, it would have been quite adaptive because they would have gotten a great pleasure out of food and they would have been the ones to pack on the pounds and survived longer. But it doesn't work so well in this environment."

Dopamine linked to motivation

Back at Queen's University in Kingston, Ont., Richard Beninger is watching a series of videos of laboratory rats on a chin up bar, taken by his students. When a normal rat is placed on the bar, it gets down immediately. But something amazing happens when researchers give the animal a drug that blocks the dopamine receptors. Now the rat stays on the chin up bar, longer and longer after every dose.

"The animal will just sit there if their dopamine is blocked. It's not that they can't move, they are just not motivated to move," Beninger said. "It seems that you need dopamine to engage in the environment."

"I'm still struggling to understand the implications of this condition, 'catalepsy,' he said. But he calls it an exciting finding. "I think there's some new, valuable information in this phenomenon."

"I think the cues that are around us, the things we interact with day to day, all that we are able to respond to, pick up, and handle, all that requires a certain level of dopamine. And if we repeatedly are exposed to stimuli, with dopamine reduced, we lose our ability to respond to those particular stimuli. It seems that dopamine gives you a reason to move, get off the bar, act on a stimuli, and without it, you have no interest in reacting the stimuli or environment."

Beninger says it resembles the movement disruption in people with Parkinson's disease, which is associated with reduced dopamine activity, something he is also studying in his lab.

Dopamine's role in relationships

Beninger is also studying how dopamine shapes our relationships. It seems that when someone is nice to us, our dopamine will draw us back to that person.

"So when I interact cooperatively with someone else and they interact cooperatively with me, that person, which is a representation in my brain, by the action of dopamine, gains an enhanced ability to attract me in the future," Beninger says. "So the dopamine sculpts our social landscape."

I think it's an absolute marvel, you can only marvel more as you begin to learn more about the chemical neuroanatomy of the brain," Beninger says. "It's all of that working together that creates my mental experience, my whole life. It's an absolute marvel."

If they understand brain chemistry neuroscientists believe they will be able to offer therapies to fight mental illness and improve the entire human experience. And Dr. Eric Kandel says discoveries are inevitable, in part because there are now so many scientists in the field.

"When I was a medical student, I wanted to take an elective in brain cell science, but there was only one lab in New York City that had a good person I could work with. It was unheard of. Now you go in the street and every other person you meet is doing brain science."

" I was working in a lab for the first time in 1955. By 1969, a society had formed in North America, called the Society of Neuroscience, and it had 600 members. Now it has 35,000 members. The number of people now working in brain science has grown enormously. It's gone from an arcane discipline. Now it's one of the most exciting, if not the most exciting area in biology."

This is part two of a four part series called Inside Your Brain on CBC's The National, World at Six and CBC.ca exploring how modern neuroscience is changing the way we think about the way we think. In part three Kelly Crowe discovers that our brains are highly active even when we perceive them to be idle and the idle brain may be the key to conciousness. The research for this series was funded by a Canadian Institutes of Health Research journalism award.

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