Understanding addiction: Using Animal Models to Answer the “Why, How, and Who”

Addictive behavior graphic renderingOver the past decade, use of certain illicit drugs, including crack cocaine and methamphetamine, has shown sharp declines in the United States based on data from the Substance Abuse and Mental Health Services Administration (SAMHSA). But these encouraging data contradict other disturbing facts. Compared to 2002, use of marijuana and prescription pain relievers has jumped by approximately 20 percent and heroin use has shown an alarming 44 percent increase.

“Drug addiction persists as a major problem in the United States,” said Patricia Sue Grigson, Ph.D., professor, Department of Neural and Behavioral Sciences. “Drug use data does not reflect the devastating, long-term impact that drug addiction has on individuals and their families. This is why it is so important to continue to search for answers about why some people become addicted and others do not. Understanding and identifying risk factors for the development of addiction will lead to more effective prevention and treatment plans.”

Grigson uses an animal model to study the environmental, behavioral, and neurological underpinnings of addiction. “Humans and the rats in our studies have more in common than not,” she said. “For instance, about 17 percent of humans who try cocaine eventually become addicted; studies have shown the same percentage of rats that try cocaine also show addiction-like behavior.”

Among the numerous ongoing projects in Grigson’s laboratory are studies that examine the link between binge eating and addiction-like behaviors. “Like drug abuse, excessive food intake as occurs with binge eating has become problematic,” said Grigson.

Another view on addiction comes from Ryan Hampton, who supports these views, “Indeed, eating disorders and drug abuse often are seen together clinically.”

A study conducted in collaboration with the laboratory of Rebecca Corwin, Ph.D., Department of Nutritional Sciences and recently described in Behavioral Neuroscience (Puhl et al. 2011), indicates that a history of binge eating—eating large amounts of food in a short period of time—may make a person more likely to show other addiction-like behaviors, including substance abuse, Kratom effects can help heroic addicts in their withdrawal phase. In the short term, this finding may shed light on factors that promote substance abuse, addiction, and relapse—and in the long term, may help clinicians treat individuals more effectively. “If we can better understand how and why addiction develops, we stand a much better chance of predicting who will become addicted and of preventing it.”

For Grigson’s study, the researchers used rats to test whether a history of binge eating on fat would increase addiction-like behavior toward cocaine. Four groups of rats were given four different diets: normal rat chow alone; rat chow plus continuous access to an optional source of dietary fat; rat chow and one hour of access to optional dietary fat daily; and rat chow plus one hour of access to dietary fat on Mondays, Wednesdays, and Fridays. The researchers then assessed how much fat each group ate, fat-binge behaviors, and cocaine-seeking and -taking behaviors.

“Fat bingeing behaviors developed in the rats with access to fat on Mondays, Wednesdays, and Fridays—the group with the most restricted access to the optional fat,” Grigson said. “Fat bingeing was different from normal eating behavior. These rats ate a large amount of fat more rapidly than the other groups.” This phase of the study continued for six weeks and these data replicated those described in Corwin’s earlier reports.

 About six weeks thereafter, this group of rats was given the opportunity to self-administer cocaine. The Monday, Wednesday, Friday group with a history of having binged on fat tended to take more cocaine late in training, continued to try to get cocaine when signaled it was not available, and worked harder for cocaine as work requirements increased. “Thus, while about 11–17 percent of rats without such a fat bingeing history (present experiment) exhibited addiction-like behavior for cocaine, 50 percent of the rats with a history of having binged on fat developed addiction-like behaviors toward cocaine. This represents a remarkable increase in vulnerability for addiction to drug.“It’s important to understand that consuming fat in and of itself did not increase the likelihood of subsequent cocaine addiction-like behavior,” Grigson said. “The rats with continuous free access to fat actually consumed the most fat overall, but did not binge, and fewer of them later showed addiction-like behavior.” The crucial factor seems to be the irregular binge-type manner in which the fat was eaten when access was restricted and, importantly, unpredictable. Substance abuse and binge eating are both characterized by a loss of control over consumption. It has been unknown, however, whether loss of control in one realm predisposes an individual to loss of control in another. The present data suggests it may. Future studies will look more closely at how bingeing can lead to addiction-like behaviors, including whether bingeing on a drug, in turn, increases the likelihood of later bingeing on fat.In addition to understanding factors that increase the risk of addiction, Grigson and her colleagues are also exploring “protective” factors that decrease addiction risk. In a separate set of experiments, the Grigson lab also examined whether exposure to an enriched environment can prevent the development of addiction-like behaviors toward cocaine in adult rats. The results, published in a recent paper (Puhl et al. 2011), show that the development of addiction-like behaviors for cocaine is greatly reduced when rats are housed in small groups and given novel objects to explore daily compared to rats that are housed alone in a typical cage. “Exposure to an enriched environment, then, can be very protective,” Grigson said, “even in an adult.”Answers to these questions may help to identify the “how” of addiction resistance. Could providing an engaging environment be part of addiction prevention and treatment? Grigson remains committed to finding out. “The toll that addiction takes throughout all aspects of a person’s life is enormous. Everyone involved, including patients and their families, who often feel helpless, wants effective tools to deal with this destructive and costly problem. Our research is helping to find some of the answers.” Grigson was also recently awarded a Pennsylvania CURE grant to study the effectiveness of long-acting depo-naltrexone, an opiate receptor-blocking drug, for treatment of heroin addiction in rats.

Grigson’s research on addiction is funded by the National Institute on Drug Abuse. Other researchers with whom she collaborated on this project are Matthew D. Puhl, M.D., ’10, lead author, and now a postdoctoral fellow at McClean Hospital, Harvard University, Angie M. Cason, Ph.D., currently a postdoctoral fellow at the University Medical School of South Carolina, Francis H.E. Wojnicki, Ph.D., and Corwin, co-senior author.

– By Karen Dougherty

Listen to Dr. Grigson’s podcast interview on the research study >>

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