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anatomy of a study

ROBERT F. BUKATY/The Associated Press

One of this year's Gairdner Award winners, Cal Stiller (who helped found MaRs Discovery District in Toronto), said this week that Canada lacks the venture capital needed to finance research for groundbreaking treatments. Part of the problem may be that it's hard for the layman to understand - and hence be invested in - a research project. With apologies to the scientific community for oversimplification, Globe Focus deconstructs one such undertaking. It starts, as many studies do, with a pair of mice, and may have applications even *wink* *wink* for Tiger Woods syndrome.





The Researcher

As golf fans and celebrity followers watched the disgraced Mr. Woods return to the pro circuit this week, they were still asking: What was he thinking? Min Zhuo wants to find out. Dr. Zhuo, 45, is the first EJLB-Michael Smith Chair in Neuroscience and Mental Health (named in 2003), studying the neurobiology of pain, pleasure and emotion, at University of Toronto. He investigates the physiological processes involved in sexual attraction in the hopes of developing new ways to treat chronic pain. He also holds the Canada Research Chair in the Neurobiology of Pain and Cognition. He arrived in Toronto from Washington University in St. Louis, Mo., in July, 2003.

The Pilot Light (how an idea gets started)

Dr. Zhuo decided to tackle the neurological basis of sexual attraction after a curious observation on a two-hour flight eight years ago. He settled into the aisle seat next to an unresponsive and tense-looking man who barely acknowledged his hello. But when a tall, attractive blond woman arrived to claim the open window seat, the man's character changed completely: He greeted her warmly, asked her name, helped with her bag and chatted up a storm for the entire trip. Dr. Zhuo wondered just what switch had been flipped in the man's brain to prompt such a dramatic alteration in his personality.

The Reasoning

The dramatic about-face of the airplane passenger reminded Dr. Zhuo of a study he had heard about in his university days: Patients suffering from long-term pain were allowed to self-regulate the dosage of their morphine drip. The researchers found that men being cared for by nurses they found attractive required far less morphine to manage their pain than the control group.

This tight link between pleasure and pain means that understanding how the brain generates sexual feelings could have real applications in managing chronic pain. Scientists know that the brain processes both pleasure and pain in the anterior cingulate cortex, but no one knows how the ACC produces positive feelings in response to pleasurable input and negative feelings in response to pain.

Further Applications

Examining amorous minds may create possibilities that extend well beyond treating pain.

Dr. Zhuo says that with a better understanding of how neurons in certain key areas of the brain become excited, we may soon be able to treat those parts responsible for such un-role-model-like behaviour as Woods's or other celebrities.

"There's a biology basis. You can't just say they're bad people and they have to be criticized," he says. "They just cannot control it. And of course they have the money and they have the fame, and that's what happens."

If Dr. Zhuo can figure out how our brains respond to emotional stimuli such as pleasure and pain, it could be a first step toward treating all kinds of human behaviours, from manically refreshing your e-mail inbox to sticking with a dud or even abusive boyfriend against your better judgment.

"People fall into relationships, and even though it's not a good one, they can't pull out of it," he says. "But what could be the neuronal basis for that? We don't usually explore that question.

"I think if we have the animal model to understand what's going on in your brain, maybe in the future it will be a big help in treating those emotional disorders," he says over the phone from Seoul, where he is teaming up with another research group.

"In the old days, because we didn't know what was going on, we treated [the brain]as a black box," he says. "I really believe the brain can be manipulated, and if we understand it well, we can treat it well. It's not like you have a tumour and we're going to do surgery. We can treat a lot of these emotional disorders with basic science knowledge."

The First Step

Studying the molecular mechanisms behind sexual attraction. Dr. Zhuo is a groundbreaker: "We are the first group to look at synaptic mechanisms of sexual attraction in the anterior cingulate cortex" in mice.

His group placed male and female mice in a rectangular box divided down the middle by a perforated screen. The screen's holes were big enough for mice to see and smell each other, but too small to pass through.

The researchers found that with female mice on the other side, male mice spent considerably more time up against the barrier. (Conversely, female mice didn't alter their behaviour much in response to males, Dr. Zhuo points out with a chuckle.) After exposure to female mice, male mouse brains showed strong and prolonged activation in the ACC.

The Next Step

Studying whether the same neurons are also involved in processing pain or fear. Identifying the molecular pathways that trigger sexual activation, and identifying those pathways that maintain sexual memory.

The Support

The study is backed by grants from the Canadian Institutes of Health Research, as well as Dr. Zhuo's research funding, which comes with both chairs. He publishes 10 to 20 papers a year.

Marit Mitchell is a researcher at Discovery Channel Canada

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