Ethanol-loving hamsters studied by faculty and student researchers at UAA

Did you know that Siberian dwarf hamsters are working for grain alcohol over in UAA's Social Sciences Building (SSB)? Don't worry, it's for science. And they also work for chocolate.

Gwen Lupfer-Johnson, Ph.D., an associate professor for the Department of Psychology, studies operant conditioning and habituation in dwarf hamsters. "Dr. Gwen," as her students call her, began studying social learning and social transmission of food preferences among these hamsters 13 years ago. After working with the animals for years, she was surprised to discover they like the taste of grain alcohol. In fact, they like it so much they sometimes choose it over water. That came as quite a surprise. "With most rodents, you either selectively breed them — there are specially bred lines of alcoholic rats — or you do what's called sucrose fading," she says. Akin to developing a taste for alcohol by starting with sweetened wine coolers, the animals are given sweetened alcohol and then alcohol with a gradually decreasing sugar content until they end up drinking straight alcohol.

When a student, Kori Radcliffe, approached Lupfer-Johnson three years ago to act as a mentor for a project through the National Institutes of Health summer research program at UAA and told her she wanted to do dwarf hamster research relating to alcoholism, Lupfer-Johnson was skeptical. "I had never gotten these little guys drunk — it had never occurred to me," she says. "I told her, 'The thing is, Kori, we can give them alcohol if you want, but they're probably not going to drink it,' so this will just be your back-up project because it's probably not going to go anywhere.'"

They rigged up water bottles with a 10% unsweetened ethanol solution (diluted Everclear) to the cages of several hamsters. "To our surprise," says Lupfer-Johnson, "they drank to the point of falling over," a phenomenon that would later be carefully measured by another student in collaboration with Dr. Gwen using an intoxication quantifier called the Wobble and Splay Scale. No joke. More on those results in a moment.

Lupfer-Johnson and Radcliffe's surprising results to the two-month summer project, "...turned into years of alcohol research and at least four faculty at UAA putting time into studying it — myself, Dr. [Eric] Murphy, Dr. [Ian] van Tets and Dr. [Khrys] Duddleston," says Lupfer-Johnson. "I wouldn't be studying alcohol if a student hadn't said, 'I really want to study alcoholism.' I had other plans for these hamsters. That project was the spark for anybody doing alcohol study with hamsters."

The fact that the hamsters are not "tricked" into choosing alcohol is significant. "They're not food or water deprived, so they're not doing it for the calories or fluid," says Lupfer-Johnson. "They just like the taste of plain old alcohol." But why do they like it? And how do their bodies process it? Finding answers to those questions has kept Lupfer-Johnson, her colleagues in psychology and biology and several undergraduate and summer students busy for the last three years. Right now in SSB's R.J. Madigan Learning Laboratory there are five dwarf hamsters that work in operant boxes, aka Skinner boxes, turning a wheel or pressing a lever to receive an alcohol or chocolate pellet reward.

"There has to be some natural selection going on here. They must have evolved to deal with ethanol," Lupfer-Johnson says. For exploration of the evolutionary reasons behind the Siberian dwarf hamsters' high tolerance for alcohol, she sought help from within UAA's Department of Biology. Professor Khrys Duddleston, Ph.D., has shown that the way they gather and store food may be responsible.

"In nature, which is Siberia for these guys, they eat rye grass seeds. They don't just eat rye grass seeds, they hoard rye grass seeds," explains Lupfer-Johnson. Hamsters store up to several grams of food in their cheek pouches for deposit in the food caches in their burrows. "So I've provided chewed up, hoarded hamster rye grass seeds to Dr. Duddleston," she says, which, incidentally, can be a very smelly undertaking. It's not unusual, she says, to hear her yelling "I've been musked! I've been musked!" and making a beeline for the restroom on the second floor of the Social Sciences Building. (That might explain a few things for students and colleagues who've been startled in the hallways.) "These horrible little musk glands at the corners of their lips lubricate and mark everything they shove into their cheek pouches. I've done a number of studies where I've emptied their cheek pouches for one reason or another and that's when I get musked."

When Duddleston adds yeast, which, it turns out, is present even in Siberia, to the half-masticated rye grass seeds harvested from hamster cheek pouches by Lupfer-Johnson, she finds that fermentation takes place. It seems likely that the food hoards for the long Siberian winters turn in to a sort of natural home brewery. Duddleston and Lupfer-Johnson have plans to replicate the Siberian burrow conditions in the lab to further test their results. Lupfer-Johnson says, "The way they pile up their food has naturally selected for the ability to break down ethanol and also for the liking of ethanol. A hamster that didn't like the taste would starve."

Based on their current findings, Lupfer-Johnson says, "They're probably, almost certainly, adapted to alcohol consumption in the wild. It's not possible for a hamster to achieve lethal blood ethanol content from drinking alcohol. Their livers break it down so quickly that their blood never gets enough alcohol in it to become fatal."

Science tends to breed more science. It was another summer study with a student last year, creating alcohol dose response curves for dwarf hamsters, that lead Lupfer-Johnson to discover that Wobble and Splay Scale mentioned earlier. "It's an actual behavioral rating scale where you quantify how much the animal wobbles and splays. You videotape it and on a scale of 1 to 5 — zero, no wobbling, one, wobbles, but doesn't fall, two, both wobbles and falls, all the way to four or five, which is falls and can't get up," she explains. "That's where we learned that orally, [dwarf hamsters] can take a gigantic dose," she says, noting the hamsters showed little impairment at doses that were easily 10 times what a human could take.

The hamsters never seem to suffer from the ill effects of alcohol overindulgence either — no typical hangover symptoms like nausea and lethargy.

Alissa Hoskie, an undergraduate who plans to graduate next year, received a grant from the Honors College to study alcohol dehydrogenase enzymes in the super-processing livers of the dwarf hamsters for her senior thesis. "What Alissa was doing was correlating behavioral measures with alcohol dehydrogenase activity," Lupfer-Johnson says.

Hoskie's cross-disciplinary project had her spending time in the lab with Lupfer-Johnson documenting behavioral measures, including the "loss of righting reflex," which measures an animal's sensitivity to ethanol by how long they stay passed out at different doses. Alcohol was administered via injection for precision. In proof that science requires not just hand soap, but a lot of patience, Lupfer-Johnson says Hoskie spent sometimes hours waiting for signs of activity in the passed-out subjects that were lying on their backs to document precisely the return of the righting reflex, which is when they regained sufficient consciousness to get back on their feet. Then with biology professor, Ian van Tets, Ph.D., Hoskie worked in the lab to measure liver enzymes. She presented her results at the Association for Behavior Analysis International conference in Seattle. What she found has sparked, in what now seems like a clear pattern for dwarf hamster research at UAA, additional research.

Hoskie found that in female dwarf hamsters, the more alcohol dehydrogenase activity they have, the less sensitive they are to alcohol. Lupfer-Johnson explains, "The more their livers break it down, the less sensitive they are." Not surprising. "The weird thing is that's not true for the males," she says. "So we're going to keep studying that."

In addition to her work with students and with Duddleston, Lupfer-Johnson has collaborated on research with van Tets to study fatty liver disease using dwarf hamsters and with both Murphy and van Tets to study the science behind visceral obesity, or beer bellies, which is an extension of a study done by Murphy and van Tets with rats. While rats can develop a beer gut, the hamsters don't suffer from visceral obesity.

While the professors are able to resist naming the cute though "not nice at all" hamsters, which are bred from hamsters that are wild caught in Siberia, student researchers have been known to name batches of them after Disney princesses, Dungeons & Dragons characters and even the folks from the television show Friends, according to Lupfer-Johnson. On one hand, it can make distinguishing between subjects easier. Student will remember that they injected Cinderella more readily than Subject C-57. On the other hand, it can make for some interesting communication between colleagues. Lupfer-Johnson recalls sending an email to van Tets to say, "Jennifer Aniston's guts are in your freezer."

Lupfer-Johnson will continue her operant conditioning studies and classical conditioning studies with dwarf hamsters in the coming years at UAA along with her colleagues and encourages students who are interested in research to approach a professor and ask how they can participate. Students should have an appreciation for the unexpected, intellectual curiosity, patience and a sense of humor. And perhaps a favorite television show.