Cerebral Hemispheres 2
NEUROSCIENTIFICALLY CHALLENGED

NEUROSCIENCE MADE SIMPLER

Using Gene Therapy to Treat Addiction


When you take into consideration the number of ways in which it can manifest itself, addiction is probably the most prevalent mental disorder that we don’t yet have a pharmaceutical treatment for. By identifying common neurobiological substrates that underlie all types of addiction, however, scientists hope to find drug targets that may one day allow it to be treated at least as methodically as other widespread disorders like depression. One of these commonalities found in the brains of addicted subjects involves a reduction of the number of available dopamine receptors in reward areas of the brain. Specifically, the density of a receptor called the D2 receptor is found to be decreased.

This diminished D2 receptor density can lead to addiction in two ways. A normal level of D2 receptors in an area of the brain called the nucleus accumbens is thought to play an important role in regulating impulsivity, and thus in avoiding an initial exposure to large amounts of drugs (or any addictive substance). Low levels may predispose drug users not only to trying drugs, but also to using them in amounts large enough to lead to addiction.

When a drug is used, it increases dopamine transmission. Over a period of time, this increase in dopamine activity in the brain can cause D2 receptors throughout the reward system to become depleted. This occurs due to a process called downregulation, which is a natural response of the body to decrease the number of receptors for a substance if the substance seems to be available in excessive amounts. Downregulation can lead to a disruption of the reward system that causes an addict to have difficulty finding pleasure in “normal” activities. The drug is the only substance that can facilitate a sense of pleasure, and compulsive use becomes difficult to avoid.

This understanding of the role of D2 receptors in addiction led researchers at the U.S. Department of Energy’s Brookhaven National Laboratory to search for a way to increase the number of D2 receptors in an addicted brain, in the hopes that doing so could reverse the process of addiction. They found gene therapy to be a successful way to do it.

First, the scientists trained a group of rats to self-administer cocaine (not a difficult thing to do, as most organisms tend to like cocaine). They then injected an innocuous virus that carried the gene for D2 receptor production into the rats’ brains. It was hoped the virus would insert the D2 receptor gene into the cells of the rats’ reward system, leading to an increase in D2 production, and a consequent reduction in addictive behavior.

After the gene therapy treatment, the rats showed a 75 percent decrease in cocaine self-administration. The change lasted for about six days before the rats returned to their previous usage. The group at Brookhaven has conducted a comparable experiment in the past with alcohol-addicted rats, and found similar results.

D2 receptor density has been shown to play a role in predisposition to addiction, as well as in the propagation of addictive behavior after its onset. With experimental results like those seen at Brookhaven, it appears manipulating D2 receptor density may have potentially beneficial effects in treating addiction. Unfortunately, given gene therapy’s checkered past (see here), it will be quite some time before such methods become available for use with humans. Primate studies, however, will most likely be the next step, and if all goes well perhaps gene therapy may one day end up being able to treat what could arguably be called the greatest behavioral scourge of our species: the repetitive pursuit of rewards long after they’ve lost their rewarding value, a.k.a. addiction.

YOUR BRAIN, EXPLAINED

Sleep. Memory. Pleasure. Fear. Language. We experience these things every day, but how do our brains create them? Your Brain, Explained is a personal tour around your gray matter. Building on neuroscientist Marc Dingman’s popular YouTube series, 2-Minute Neuroscience, this is a friendly, engaging introduction to the human brain and its quirks using real-life examples and Dingman’s own, hand-drawn illustrations.

  • An informative, accessible and engaging book for anyone who has even the slightest interest in how the brain works, but doesn’t know where to begin. - Dean Burnett, PhD, author, Happy Brain and Idiot Brain

  • Reading like a collection of detective stories, Your Brain, Explained combines classic cases in the history of neurology with findings stemming from the latest techniques used to probe the brain’s secrets. - Stanley Finger, PhD, Professor Emeritus of Psychological & Brain Sciences, Washington University (St. Louis), author, Origins of Neuroscience

  • Dingman weaves classic studies with modern research into easily digestible sections, to provide an excellent primer on the rapidly advancing field of neuroscience. - Moheb Costandi, author, Neuroplasticity and 50 Human Brain Ideas You Really Need to Know

  • ...a highly readable and accessible introduction to the operation of the brain and current issues in neuroscience... a wonderful introduction to the field. - Frank Amthor, PhD, Professor of Psychology, The University of Alabama at Birmingham, author, Neuroscience for Dummies

BIZARRE

This book shows a whole other side of how brains work by examining the most unusual behavior to emerge from the human brain. In it, you'll meet a woman who is afraid to take a shower because she fears her body will slip down the drain, a man who is convinced he is a cat, a woman who compulsively snacks on cigarette ashes, and many other unusual cases. As uncommon as they are, each of these cases has something important to teach us about everyday brain function.

  • Through case studies of both exceptional people as well as those with disorders, Bizarre takes us on a fascinating journey in which we learn more about what is going on in our skull. - William J. Ray, PhD, Emeritus Professor of Psychology, The Pennsylvania State University, author, Abnormal Psychology

  • A unique combination of storytelling and scientific explanation that appeals to the brain novice, the trained neuroscientist, and everyone in between. Dingman explores some of the most fascinating and mysterious expressions of human behavior in a style that is case study, dramatic novel, and introductory textbook all rolled into one. - Alison Kreisler, PhD, Neuroscience Instructor, California State University, San Marcos

  • Bizarre is a collection of stories of how the brain can create zombies, cult members, extra limbs, instant musicians, and overnight accents, to name a few of the mind-scratching cases. After reading this book, you will walk away with a greater appreciation for this bizarre organ. If you are a fan of Oliver Sacks' books, you're certain to be a fan of Dingman's Bizarre. - Allison M. Wilck, PhD, Researcher and Assistant Professor of Psychology, Eastern Mennonite University

  • Dingman brings the history of neuroscience back to life and weaves in contemporary ideas seamlessly. Readers will come along for the ride of a really interesting read and accidentally learn some neuroscience along the way. - Erin Kirschmann, PhD, Associate Professor of Psychology & Counseling, Immaculata University