A Peek into Psychopharmacology: Rats on Drugs

Born in Russia, Andy Verendeev didn't end up at American University in Washington, DC like most students do. After moving to Istanbul, Turkey at age 18, a country where he knew no one and could barely speak the language, he found a job and enrolled in a Turkish language school. "It was an adventure, it was great. By the end of the first year I decided I wanted to stay in Istanbul and go to college", Andy reflects.

While at Bogazici University, one of Turkey's leading research universities, his interest in experimental psychology flourished when he began working in two labs at the end of his first undergraduate year, studying animal models of depression and sexual conditioning in quail. "The more I read, the more I became interested in biological psychology," Andy says. Serendipitously, Andy mentioned a desire to study in America to a professor at Bogazici who happened to be a friend of Anthony Riley, the chair of the department of psychology and director of the psychopharmacology lab at AU. Temporarily suspending his undergraduate studies at Bogazici, he packed his bags and headed for America's capital.

"As an undergraduate in Turkey, he took time off from school to volunteer in my laboratory for three straight summers (at his own expense). During his visits, he was active in research and co-authored several journal papers and presentations at national conferences. He was constantly engaged [in his work] and interested," says Anthony Riley. "Simply put, he is a smart fellow. He reads voraciously and simply loves to talk about science. There are few sure bets in our work; he is one of them."

Andy is currently pursuing his PhD in behavioral neuroscience at American University. Supported by a grant from the Andrew W. Mellon Foundation, his research involves examining factors that might be related to the susceptibility to use and abuse drugs. In particular, he is focused on the relationship between aversive and rewarding effects of drugs. "He is looking at these factors and how they might interact to impact initial drug taking, and how they might vary with a host of conditions to increase the likelihood of drug use," said Anthony Riley. Current statistics show that drug abuse and drug-related mortality continue at considerably high levels in the US. Advancing scientific understanding of drug use and abuse at the neurobiological level is an important step toward greater capacity to reduce its negative consequences on the individual and society.

Originating in the 1920's from Ivan Pavlov's experiments with dogs, reward and aversion are components of what is broadly known as classical conditioning. Conditioning in animals occurs when a neutral stimulus (in Pavlov's case a bell, which has no inherent meaning to a dog) is paired closely in time with a meaningful stimulus, such as food. The term "reward" describes a stimulus that has a positive meaning, while "aversion" describes a stimulus with negative meaning. The animal learns to associate the neutral stimulus with the meaningful stimulus, and will eventually display certain behavior corresponding to the neutral stimulus. The dogs learned to associate the bell with food, and eventually began salivate immediately after hearing the bell. When the meaningful stimulus is a complex compound with multifarious effects on the brain, such as a drug, the lines between reward and aversion become muddled.

Working with morphine and rats, Andy combined two specific methods: conditioned taste aversion (CTA) and conditioned placed preference (CPP). These allow him to measure specific motivational effects of drugs; CPP is a measure of drug reward and CTA is a measure of drug aversion. Over several trials, he paired morphine with saccharin (an artificial sweetener) and injected rats with the drug. Following conditioning, rats learned to avoid saccharin because it became associated with the aversive effects of morphine. "It's the discomfort of the novelty of the drug state and some aversive property of the drug that rats don't like," explains Andy. Additionally, (the same) rats injected with morphine also displayed a continued preference for an experimental chamber that was paired with the drug, as measured by CPP. "People abuse drugs because the reward outweighs the aversion. My data show that rewarding and aversive effects occur at the same time," he said. In the second phase of the experiment, Andy attempted to extinguish the newly acquired CTA and CCP in the rats.

Conditioned Taste Aversion and Conditioned Placed Preference are common experimental procedures used in behavioral psychopharmacology research. Placing animals injected with a rewarding drug in a chamber with distinctive environmental cues leads animals to develop an association between the pleasant, feel-good effect of the drug and the specific environment in which the effect is experienced. In contrast, the CTA procedure conditions animals to learn the association between a novel taste and the unpleasant, displeasing effects of a (otherwise rewarding!) drug, and learn to avoid the taste in the future. Taste aversions are also observed in humans, for example when taste is accompanied by gastrointestinal illness.

Verendeev's research highlights the complexities of how reward correlates with aversion. "The data suggests that there might be a common brain mechanism mediating both aversive and rewarding properties of the drug," he concludes. After neuroscience, Andy's other scientific interest is evolution, particularly the mechanisms of evolution, a topic that he also hopes to do research in someday. As for plans to go back to Russia, "I haven't been to Russia in a long time, I have no plans to go back. I love what I am doing here", he says.

Written by Nadia Ramlagan

Reviewed by Nira Datta

Published by Pooja Ghatalia

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