Discover 2012

Every spring DISCOVER: Marquette University Research and Scholarship showcases some of the most interesting research happening on Marquette's campus. Learn more through the links below.

F or the most part, human motivation is intuitive. From the anxiety of a looming deadline to the enticement of a cash bonus, positive and negative scenarios are powerful and obvious motivators that dictate how giving the rats quinine, a bitter liquid, resulted in decidedly unfavorable expressions. Needing more than mere facial reactions, Wheeler also measured fluctuations in dopamine, a key neurotransmitter in the brain responsible for a wide variety of behavioral and cognitive functions, including reward and motivation. Using a technique known as fast-scan cyclic voltammetry, Wheeler was able to measure dopamine concentrations, in real time, in one of the brain’s reward centers known as the nucleus accumbens. Not surprisingly, the rats’ dopamine levels spiked significantly immediately after the Kool-Aid treat. Turning back to addiction, Wheeler then wondered: How would the animals react to the Kool-Aid when paired with an infusion of cocaine? Taking a prompt from the Pavlovian playbook, Wheeler taught the rats that they would receive cocaine (something they enjoy) immediately after the Kool-Aid (something else they enjoy). Over time, the rats’ dopamine levels measured incredibly low after the administration of the sugary drink. Further, they showed decreased reward sensitivity and displayed visually aversive behaviors, such as negative facial expressions. The rats were also given a differently flavored, but similarly sweet, concoction, which resulted in increased dopamine and favorable behaviors. Only the Kool-Aid, which they now associated with cocaine, caused a negative reaction. “It seems counterintuitive, but essentially the cocaine changes the way the rats feel about the Kool-Aid,” Wheeler says. “What they once loved, they now have no taste for.” Wheeler’s findings, published in 2011 in Biological Psychiatry, counter previous research contending that a stimulus associated with cocaine causes an increase in dopamine and a pleasurable feeling in rats, suggesting that the positive feelings promoted drug seeking. “This is important for recognizing and hopefully avoiding the complex psychological forces that cause relapse in cocaine addicts,” Wheeler notes. But the significance of his work extends beyond combating addiction. Associations are environmental influences that infiltrate everyone’s lives, and Wheeler suggests that negative emotional influences promote other undesired behaviors, such as compulsive overeating and gambling. “We examine decreased dopamine release, reward insensitivity, and drug-seeking behaviors as a way to understand how our environment changes our emotional state and our behavior,” he says. “The next step will be figuring out what we can do about it.” Wheeler adds, “The true value of this work, we hope, is that it contributes to a more complete understanding of the human condition.”² Marquette University 13 we respond to a given situation. Behaviorists, like the noted B.F. Skinner, have long studied the ways in which positive reinforcement affects human behavior and cognition. Dr. Robert Wheeler, an assistant professor of biomedical sciences at Marquette, is interested in negative affective states, those “bad feelings,” which he posits impact life the most. And his research has uncovered a counterintuitive relationship between positive and negative reinforcement in cocaine addicts. “Positive reinforcement is the best way for us to learn. However, the negative has a profound influence on life,” Wheeler says. “But we don’t have a good neuroscientific understanding of it.” Wheeler focuses his research on what he calls “the tragedy of addiction,” a disease marked by a cycle of abstinence and relapse. The relapse, he says, is normal human behavior; however, it’s also the most tragic part of the disease. “As addicts use more and more, they stop doing things they enjoy,” Wheeler says. “They are pushed in one direction at the exclusion of everything else they used to love.” This study of reward-seeking behavior, known as “hedonics,” is helpful in understanding the behavior of those addicted to cocaine and other narcotics. More important, he says, it can help unravel the intricate neurological circuitries and chemical signals that cause these behaviors. And better understanding the neurophysiology of addiction could lead to improved clinical treatment options. To measure hedonics, Wheeler turned to the same subject that Skinner did: the rat. As a baseline, he first examined how the animals reacted to something they enjoy — in this case, Kool-Aid. The saccharine-infused water garnered positive facial expressions and mouth movements, which Wheeler says are relatively universal among mammals. On the other hand,