Until indoor smoking bans started popping up in cities across the country in recent years, smoke-filled bars were a fixture of American culture, smoking and drinking entwined like the peanut butter and jelly of vices. If you were a casual scientist of the street, you might have hypothesized that there was something meaningful behind the common sight of the barfly with a drink in one hand and a cigarette in the other. And laboratory research has mostly supported that anecdotal evidence, with study after study showing that alcohol does in fact promote smoking behavior, while larger surveys have found alcoholics more likely to be smokers and vice versa. But where do the effects of a beer and a cigarette meet in the brain, such that ordering up one raises a person’s desire to partake of the other?

That’s been one of the questions studied in the Clinical Addictions Research Laboratory at the University of Chicago Medical Center, where director Andrea King has examined the phenomenon of alcohol-induced smoking. The studies put the spotlight on an interesting population of smokers - not the pack-a-day regulars, but those who smoke “socially,” a few cigarettes on nights out on the town with friends. That’s a demographic that hasn’t received as much study as addicted smokers, King said, in part due to psychiatric guidelines that classified people as either smokers or non-smokers with no space for people in the gray areas.

“Older studies wouldn’t even ask how frequently subjects smoked; if they smoke, they must be addicted, daily smokers,” said King, an associate professor of psychiatry and behavioral neuroscience. “But we see this percent that seems to be increasing in subsequent surveys…about 20-30 percent would be non-daily smokers. Some of these people may continue and become vulnerable to being a chronic habitual user, or this may be a new subclass of smokers.”

King was drawn to social, alcohol-induced smoking behavior when she was attempting to recruit heavy drinkers who were not smokers for a control group, a task she found exceptionally difficult. With rates of smoking among alcoholics as high as 75 percent, the non-smoking drinker was a rare breed, so King decided to flip it around to study what causes the two behaviors to frequently co-exist.

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I spent part of last week on vacation from science in Las Vegas, where I thankfully avoided financial ruin due to some fortunate combination of genes, math awareness and a wife that has no interest in gambling. Sure, I dabbled a bit in games of chance, but as soon as I got a little bit ahead on the blackjack tables I ran for my life, knowing that the probability would even out hard in the long run. For those concerned about the financial well-being of Sin City, they still managed to turn a profit on us, thanks to the low-return temptations of fine dining and French circus acts set to Beatles megamixes. But most of our time was spent on the free entertainment of people-watching and stuff-watching, observing row after row of people almost hypnotically at work on loud, noisy slot machines amid fake New York, Paris and Venice scenery.

It doesn’t take a PhD in neurobiology to conclude that slot machines are designed to lure people into a money-draining repetition, just as it doesn’t take expertise in the casino business to realize slots are absurdly profitable - there’s a reason why they outnumber table games 100-to-1. But I wanted to go back to the scientific literature to confirm a faint glimmer of information I retained from graduate school, specifically that slot machines are masterful manipulators of our brain’s natural reward system. Every feature - the incessant noise, the flashing lights, the position of the rolls and the sound of the coins hitting the dish - is designed to hijack the parts of our brain designed for the pursuit of food and sex and turn it into a river of quarters. Or so I remember.

Fortunately, there is a robust amount of research into why slot machines are so addictive, despite paying out only about 75% of what people put in. They are, some scientists have concluded, the most addictive of all the ways humans have designed to gamble, because pathological gambling appears faster in slots players and more money is spent on the machines than other forms of gambling. In Spain, where gambling is legal and slot machines can be found in most bars, more than 20.3 billion dollars was spent on slots in 2008 - 44% of the total money spent by Spaniards on gambling last year.

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And so Neuroscience 2009 comes to an end, and it’s time to put away my badge, rest my weary feet and note-taking hand and think about biology below the neck again. Here’s the final installment of our live coverage, but come back tomorrow for a roundup of the conference with highlights, loose observations and links to other people’s thoughts on the conference. Thanks for reading!

2:30 PM - The Final Talk

The schedule may say that Neuroscience 2009 runs through the end of the day today, but judging by how many suitcase-toting scientists were jumping in airport cabs this afternoon, a small portion of the 30,000+ attendance makes it to the very end. Indeed, even the main stage ends its conference early, shutting down after a talk by Mt. Sinai School of Medicine’s Eric Nestler, an expert in the field of molecular psychiatry.

Nestler’s research focuses on the gritty details of how drugs of abuse change the expression of a person’s genes - yes, it was another addiction talk, and the former addiction researcher that I am, it was great to see the topic getting so much attention this year. In the addiction press conference I attended yesterday, Nestler hinted at a bombshell idea - frequent users of addictive drugs such as cocaine, heroin or alcohol may change the mechanics of their genes so permanently, the modifications could be passed on to their children. This “inheritable addiction” has already been observed in lab rats, Nestler said, mirroring similar results seen with the offspring of obese rats (which I talked about on Monday).

But that data must be too fresh for mass consumption, despite Nestler telling a roomful of reporters about it the day before. His talk today focused on the steps leading up to that discovery, carefully examining how repeated cocaine increases or decreases the activity of hundreds of genes in the reward pathway of the brain. Those long-lasting changes, which can cause cells of the reward pathway to actually grow and change shape, help explain why addiction is such a difficult condition to treat - it may require a complete re-re-structuring of the brain.

Much of the addiction research I’ve talked about this week has taken place in animals, but before Nestler’s talk, I came across a rare experiment that looks at the behavioral effects of a commonly-used drug in humans. It might seem strange that we know a ton about the specific genes that are up or down-regulated by cocaine, but not so much about its effects upon humans, but that’s due to procedural reasons - it’s quite hard to get approval for a study that gives illegal drugs to humans.

Michael Ballard, from the University of Chicago laboratory of Harriet DeWit, was trying to fill in at least one of those gaps in the research by testing the effects of THC (the active ingredient in marijuana) to presumably eager volunteers. Ballard then tested the subjects’ ability to judge facial expressions and determine the emotional content of pictures and personality trait words while they were under the influence of the drug. Interestingly, higher doses of THC caused the subjects to misjudge the facial expressions they were shown, suggesting an effect of the drug on social perception. The other tests were normal during the drug effect, but when brought back to the laboratory a week later, the subjects showed a decreased ability to remember neutral and negative personality traits, possibly indicating that their memories of the drug effect were biased toward happier stimuli. Ballard hopes to continue that research into other drug types - he’s currently testing amphetamine - to give the field of addiction research much-needed, laboratory-controlled human data to make sense of the flood of animal experiments.

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6:45 PM - The Opposite of a History Lesson

Eric Kandel is 80 years old, was present at the first Society for Neuroscience meeting in 1969, is 9 years removed from winning the Nobel Prize for physiology and medicine. He’s also so well known at the Neuroscience meeting, he can go by one name, “like Bono,” said SfN president Tom Carew in his introduction to tonight’s Presidental Lecture. So you might have expected Kandel’s talk to be a history lesson, a retelling of how he uncovered the cellular chain of events that underlie learning and memory in sea slugs, fruit flies, mice and, by extension, you and me.

But Kandel, looking like The Sopranos’ Uncle Junior and speaking with Woody Allen’s Brooklyn accent, had very little interest in looking back. After 75 minutes of him excitedly flashing through graphs and figures explaining recent findings in his laboratory at Columbia University, he could only narrow his talk down to four conclusions. My thesis adviser, who was sitting next to me, leaning over and whispered in amazement, “these aren’t conclusions at all, he’s still forging ahead.”

That relentless drive in someone so late in his career was infectious. Kandel said the goal of his talk was to explain how a person remembers his first love for the rest of his life, as if that was a simple quest, but his lecture portrayed science as it should be: a never-ending story, with each answer giving birth to several more questions. While some researchers settle on a single technique and pass the torch to younger researchers when the limits of that technique are reached, Kandel proved that he has stayed on the cutting edge of science, bringing fresh talent into his lab to apply new tools to his endless questions about how neurons encode memory.

As a result, almost a decade after his Nobel victory, Kandel was excitedly telling 10,000 of his colleagues about a new cellular signal, called CRB-3 in mice, which he humbly described as “a new class of functional proteins” and “an entirely new model of synaptic plasticity.” The work was backed up with the latest in genetic, cellular biology and imaging evidence, testimony to both Kandel’s ability to keep up with the fast-moving world of science as well as the sprawling world of neuroscience itself.

“One of the wonderful things that has happened in my forty years in the society, is that neuroscience, which really was quite fragmented when I entered the field…has become a unified organism,” Kandel said.

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As described on Monday and hinted at all week, this weekend marks the start of Neuroscience 2009, the annual mega-conference of more than 30,000 neuroscientists. After years of staging the meeting in areas with distractingly nice climates such as New Orleans, Orlando and San Diego, this year should be all business with the rainy chill of Chicago keeping people indoors. But there’s still a lot of fun to be had, with big-time speakers, immersive poster sessions, the never-ending hunt for the best vendor knick-knack giveaway and the night-time socials. Because of Neuroscience’s massive size, there are a million different ways to navigate a path through the science, but here’s a quick extremely long guide to what I’m looking forward to experiencing. Remember to tune in to ScienceLife all weekend (and through Wednesday) for coverage.

Saturday: Magicians Were the First Neuroscientists

Each year one of the most interesting lectures falls under the sober heading of “Dialogues Between Neuroscience and Society,” which basically means “we invited someone from outside of neuroscience to talk about neuroscience.” At previous meetings I’ve attended, that meant hearing public figures such as the Dalai Lama and Frank Gehry offering their own perspective on the brain, the mind and thinking - necessary reminders that the microscopic neurons those 30,000 scientists are concentrated on actually add up to some pretty amazing things in practice. 

This year’s Dialogues speakers are neuroscientists of a different sort: magicians Apollo Robbins and Eric Mead. Even though I saw a local version of this talk earlier this year with Robbins and neuroscientist Susana Martinez-Conde (which I wrote about it for the Tribune), I’m excited to see it again, because it really is a neat demonstration of how magicians have used the brain’s limitations to produce convincing illusions. Robbins, whose act is centered on his considerable abilities as a pickpocket, is a master of using diversion to direct a person’s attention one direction while he slips off their watch from another angle. As Robbins and Martinez-Conde explained back in January, this deceptively simple trick actually says a lot about how the brain shifts attention from stimulus to stimulus, and how a normal brain is “tricked” may help us learn about the neurobiological process that underlie an attentional disorder like ADHD. You can watch a video of a similar symposium organized by Martinez-Conde back in 2007 called “The Magic of Consciousness” - which includes Teller of Penn & Teller in a rare speaking role.

Also Saturday: We’re only two weeks away from the University of Chicago’s big Darwin conference, but I still will probably take in at least part of the symposium on Evolution of Brain and Behavior. Harvard’s Elizabeth Spelke caps off the day with a lecture on how the brain processes math - thankfully, it’s scheduled early in the conference, before my own brain will surely grow too tired to handle such a heavy topic.

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A mere fraction of the SfN poster session chaos (image from University of Wisconsin)

This weekend, a swarm of brain scientists will descend upon Chicago for one of the world’s largest annual  scientific meetings: Neuroscience 2009. More than 30,000 people will pack themselves into McCormick Place on the Near South Side to hear speakers like new NIH director Francis Collins, view scientific posters in a room the size of multiple football fields, check out the latest in laboratory and medical technology and (most importantly, for some) mingle their way through a multitude of nighttime socials. In my former life as a scientist, I attended a half-dozen of these meetings, and always found it to be a gluttonous experience - sort of the neuroscience equivalent of Thanksgiving dinner. This year, I’ll be soaking in the conference from a writer’s perspective, and will be blogging frequently during the conference’s Saturday through Wednesday run.

To whet your appetite for the latest in brain science, I’ll spend most of the week talking about some exciting neuroscientific research happening here at the University of Chicago. Purely by coincidence, there are a handful of interesting new findings from researchers in our neurobiology program hot off the scientific journal press, and I’ll feature a couple of those studies this week. Today, you’ll hear about a study that combines genetics, behavioral observation and electrophysiology to reveal an important component of how the brain changes and learns. Later this week, I’ll preview an upcoming lecture on the neurobiology of humor and discuss how eating chocolate chips reduces pain. Then I’ll round up some of the more exciting talks and events in store for this year’s edition of Neuroscience, including a gathering of researchers who study the “reward” neurotransmitter dopamine that will likely include some self-experimentation, if you will.

In the meantime, if you’d like a taste of the Neuroscience experience, here’s a long, rambling, slightly profane piece I wrote about the conference in Atlanta three years ago.

Convincing people to stop smoking is no easy task, as family members or friends of smokers know all too well. But consider a situation where roughly three-quarters of active smokers find themselves ready to quit, willing to make that all-important first step of deciding to go smoke-free. When is this short window of vulnerability and motivation open? The time is when a smoker is in the hospital, said Dr. Lisa Shah, instructor in the section of hospital medicine at the University of Chicago Medical Center, a time when the patient is also surrounded by the infrastructure needed to nurture a desire to stop smoking into a successful change of behavior.

But Shah, a researcher focused on studying inpatient tobacco cessation, said in her Medicine Grand Rounds presentation Tuesday afternoon that many doctors miss this opportunity to help their patients kick a dangerous habit. In fact, it was right there on a slide titled The Missed Opportunity, which laid out why inpatients find themselves ready to quit: the no-smoking policies in place at hospitals*, the shock of being hospitalized for an illness that may be a direct result of smoking, and the isolation from environmental cues at home or work that may trigger the urge to smoke.

“For the smokers we see here, often one big barrier to quitting smoking is that they have family members and friends who also smoke cigarettes, Shah said. “Social smoking is a huge impetus to smoke, and makes it hard to quit. So hospitalization helps them succeed in quitting smoking without the temptation.”

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Have you heard of 3,4-Methylenedioxymethamphetamine? Maybe its acronym MDMA? Or perhaps its more common street name, ecstasy? Though it’s a drug that has been used recreationally for decades, long enough to be the inspiration for books and songs, ecstasy remains scientifically mysterious, with most of the research focusing on harmful long-term effects to users’ brains. Left unanswered is a key question about ecstasy: why do people take it?

Far less research has been devoted to ecstasy’s unusual effects, which include an increased sense of friendliness, empathy and sociability in users. MDMA is closely related chemically to the drugs methamphetamine and mescaline, but the psychological effects of those drugs are very different: hallucinogen and stimulant effects may be caused by ecstasy, but are not the primary desired effects people seek out by taking the drug.

Feelings of empathy and sociability are also difficult concepts to measure in animals, where most drug research is still performed for legal and ethical reasons. How do you determine whether MDMA makes a rat “friendlier” with other rats? One method, employed in a 2005 study, measured the likelihood of rats to lie next to each other, sort of a cuddle test. Sure enough, a dose of MDMA increased the likelihood that rats who had not previously met would lie next to each other.

But the human relevance of watching rats cuddle is, suffice to say, limited. So Gillinder Bedi, as a post-doctoral fellow in the laboratory of University of Chicago professor of psychiatry Harriet de Wit, designed experiments to test the effects of ecstasy on people’s subjective feelings and the way their brains process the emotions of other people. The first of two papers on the subject was published last week in the journal Psychopharmacology.

“There is only so much you can glean about social experiences from an animal,” Bedi said via e-mail from Australia. “I think it is a fascinating drug in terms of its effects on social behavior and function, in particular given that these social effects appear to be a fundamental part of the reinforcing effects of the drug. So, in this way ecstasy gives us a window into a broader issue, which is how drug effects and social factors interact at a more biological level, and whether such interactions are an important part of why people use drugs.” read more

The death of Michael Jackson has made its expected transition from a celebration of his life and music to an uncomfortable public autopsy of how he died. More than a month after his death, the official coroner’s autopsy has yet to be officially released, but various media outlets have sniffed out one particular drug that is expected to appear in the pop star’s toxicology report: the general anesthetic propofol.

The widely-used but little-discussed drug has provoked a number of “what is Propofol?” news segments, including a piece by ABC’s Primetime: Crime that brought a camera crew to the University of Chicago Medical Center earlier this week. That segment, reported by former MTV newsman Chris Connelly aired Wednesday night, and you can watch it here.

For 30 seconds (from -2:17 to -1:47) of the video, you’ll hear briefly about research by Avery Tung, associate professor of anesthesia and critical care for the Medical Center (you will also see a rat being anesthetized with a completely different drug, halothane). In the early part of the decade, Tung conducted an NIH-funded research project examining relationships between sleep and anesthesia, and published several papers and scientific abstracts looking at how propofol mimicked the effects of actual sleep. After Tung sat down with ABC, I spent a little more time with him discussing the anesthetic and his research.

Q: First of all, what is propofol, and how often is it used?

Tung: Propofol is given intravenously to induce anesthesia in surgical patients and to provide sedation for patients in the Intensive Care Unit. It’s the most common induction agent of anesthesia in current use. It pretty much has replaced pentothal because it has fewer side effects and it makes people feel better when they wake up.

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