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Breaking the Habit of Drug Abuse

Addiction is a serious problem in the U.S. According to the National Institute on Drug Abuse, our nation spends more than $600 billion annually on problems related to substance abuse, including costs connected to health care, crime, lost work productivity and drug-related fatalities. Drug treatment programs can reduce these costs, but a significant number of individuals will continue to habitually abuse drugs despite receiving treatment, resulting in thousands of lives lost. A vast amount of research has focused on the regions of the brain that are involved in addiction, but the high rate of relapse in those addicted to drugs tells us that we don’t have a clear understanding of what makes drug addiction such a difficult habit to break. We do know that the normal learning processes that are involved in the development of regular habits are also involved in the transition from recreational drug use to the persistent and inflexible drug-seeking and drug-taking behaviors that are the hallmark of drug addiction.

To illustrate this idea, let’s say you move into a new house. You note that the light switch in your new kitchen is on the left side of the door. For the first few weeks, whenever you walk into the kitchen and it is dark, you consciously seek out and flip the light switch to the left of the door. At that time, your goal is to find the light switch to illuminate the dark kitchen and this goal controls your behavior. However, after having lived in that house for a few months, you will automatically reach to your left and flip the switch without even thinking about it. At this point, your behavior is not controlled by the goal. Instead your behavior is automatically triggered by simply walking into the dark room, with very little conscious effort on your part. In the early stages of abusing a drug, the drug-taking behavior is influenced by the rewarding properties of the drug.

In other words, your goal is to consciously seek out the drug and take it because it’s pleasurable to do so. However, as drug use progresses, the use of the drug will no longer be controlled by the conscious goal of getting high. Rather, the drug-seeking and drug-taking behaviors have become automatic and can be unconsciously triggered by cues in the environment or internal cues (such as feeling depressed).  It is at this point that the drug-seeking and drug-taking behaviors become habitual. Indeed, recent studies in both humans and animals indicate that drugs of abuse are sought not only for their rewarding properties, but also out of habit. It is thought that habits are facilitated by drugs of abuse, because drugs of abuse act on the same regions of the brain that are responsible for the development of habits. Importantly, habitual behavior is defined as behavior that persists despite negative associations or harmful consequences.

Can we break the habit? Our laboratory has identified a small region of the brain, called the patch compartment, which we believe may contribute to the development of habitual drug use. The patch compartment is a region that has numerous connections with other areas of the brain, such as those regions that interpret reward, mediate motivation and contribute to habitual behaviors. The patch compartment is a hub of sorts, where all types of information regarding reward and habits comes together and is processed and then relayed to areas of the brain that control the execution of a specific behavior.  Our research has indicated that the patch compartment is important for the development of habits.

Our initial experiments investigated whether normal habits were influenced by the patch compartment. We first trained animals to press a lever to receive a delivery of sucrose solution, over several weeks, until the animals reached a high level of lever-pressing for sucrose. Then, we trained the animals to associate the sucrose solution with a negative stimulus. In this case, we gave the animals sucrose followed by lithium, which produces gastrointestinal discomfort. After the animals had learned to associate sucrose with feeling ill, we then gave the animals the option to press the lever again to receive sucrose.

Amazingly, animals that had learned to associate sucrose with being sick still pressed the lever to receive sucrose. However, in animals without a patch compartment, there was no habitual sucrose consumption. Those animals learned how to consume sucrose, and then learned to associate the sucrose with being ill, just like the other rats. But when the patch-absent animals were given the option to press the lever to receive sucrose, they refused.

This tells us that the patch compartment is involved in the persistence of habitual behaviors. Our next step is to determine whether the patch compartment is involved in the development of habitual methamphetamine use. As we continue our research, we hope to find out more about the patch compartment and how it factors into habitual drug use. For example, is there some element in the patch compartment that can be targeted that will reduce habitual drug use? Could we someday have a compound that can be given to prevent persistent drug abuse? With the support of the National Institute on Drug Abuse, we seek to answer these questions.

This article was originally published in the Farmers and Consumers Market Bulletin Mercer Medical Moment on Wednesday, October 24, 2018.

Ashley Horner received her B.S. in Psychology from Vanderbilt University, a Ph.D. in Neuroscience at Tulane University, and trained as a post-doctoral fellow at University of Utah College of Pharmacy. Dr. Horner’s research focuses on the pathways in the brain that participate in habit formation and drug addiction. She has been a faculty member in the Department of Biomedical Sciences at Mercer University School of Medicine since 2007.