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F or the most part, human motivation is intuitive. From giving the rats quinine, a bitter liquid, resulted in decidedly the anxiety of a looming deadline to the enticement unfavorable expressions. of a cash bonus, positive and negative scenarios are powerful and obvious motivators that dictate how Needing more than mere facial reactions, Wheeler also measured fluctuations in dopamine, a key neurotransmitter we respond to a given situation. Behaviorists, like the noted B.F. in the brain responsible for a wide variety of behavioral and Skinner, have long studied the ways in which positive reinforce- cognitive functions, including reward and motivation. Using a ment affects human behavior and cognition. technique known as fast-scan cyclic voltammetry, Wheeler was Dr. Robert Wheeler, an assistant professor of biomedical able to measure dopamine concentrations, in real time, in one sciences at Marquette, is interested in negative affective states, of the brain’s reward centers known as the nucleus accumbens. those “bad feelings,” which he posits impact life the most. Not surprisingly, the rats’ dopamine levels spiked significantly And his research has uncovered a counterintuitive relationship immediately after the Kool-Aid treat. Turning back to addiction, between positive and negative reinforcement in cocaine addicts. Wheeler then wondered: How would the animals react to the “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 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 of addiction,” a disease marked by a cycle of abstinence and enjoy). Over time, the rats’ dopamine levels measured incredibly relapse. The relapse, he says, is normal human behavior; how- low after the administration of the sugary drink. Further, they ever, it’s also the most tragic part of the disease. showed decreased reward sensitivity and displayed visually “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 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 help unravel the intricate neurological circuitries and chemical the way the rats feel about the Kool-Aid,” Wheeler says. “What signals that cause these behaviors. And better understanding the they once loved, they now have no taste for.” neurophysiology of addiction could lead to improved clinical treatment options. Wheeler’s findings, published in 2011 in Biological Psychiatry, counter previous research contending that a stimulus To measure hedonics, Wheeler turned to the same subject associated with cocaine causes an increase in dopamine and a that Skinner did: the rat. As a baseline, he first examined how pleasurable feeling in rats, suggesting that the positive feelings the animals reacted to something they enjoy — in this case, promoted drug seeking. “This is important for recognizing and Kool-Aid. The saccharine-infused water garnered positive facial hopefully avoiding the complex psychological forces that cause expressions and mouth movements, which Wheeler says are relapse in cocaine addicts,” Wheeler notes. relatively universal among mammals. On the other hand, 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

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