IBBS researchers are studying how chronic drug use causes lasting changes in the brain that can lead to addiction. Their findings may aid in the development of more effective treatments for addiction.
Current addiction treatments use a combination of counseling and complete abstinence, slow weaning, or drug replacement that either substitutes for the drug or blocks withdrawal symptoms. Although these therapies control physical cravings, they don’t seem to reverse the lasting changes in the brain caused by drug abuse, and therefore may only provide a temporary fix.
During learning and memory formation, the brain’s neurons create new connections to strengthen or weaken communication routes between neighboring neurons. Similarly, chronic drug use modifies neuron connections, leading to permanent alterations in the brain’s circuitry. Taking drugs creates memories of objects, places or people that users associate with doing drugs, which triggers cravings and drug-seeking behavior when the user re-encounters those situations. Several IBBS neuroscientists study these molecular changes as they occur during learning, memory and chronic drug use.
Jay Baraban of the Solomon H. Snyder Department of Neuroscience studies how exposure to drugs like cocaine or morphine changes nerve connections. By looking at the part of the brain that controls cravings and emotional values, Baraban and colleagues have identified a protein that changes the strength of a message sent from one nerve to another. The protein determines whether the receptor for the chemical messenger glutamate is available to detect glutamate by shuttling the receptor back and forth from the cell surface. The more receptors made available at the cell surface, the stronger the message sent. Mice engineered to lack this shuttle protein exhibited persistent drug-seeking behaviors when researchers gave the mice drugs and then removed them, suggesting that the protein plays a role in addictive behaviors. Once the researchers learn more about how this protein works, they may be able to develop drugs that interact with the shuttle protein to block or reverse drug-induced changes in the brain.
Paul Worley, also from the neuroscience department, studies the molecular basis of specific forms of long-term learning and memory. His laboratory focuses on a class of proteins found at the interface between connecting neurons—synapses—that ramp up as the neurons engage in information processing and storage. These proteins directly modify the strength of the signals sent between neurons and are essential for information storage. Recent work reveals how molecules that regulate neuronal responses that signal reward, such as dopamine, can selectively strengthen communication across synapses, and implicates this process in addiction.
Mollie Meffert, a faculty member in the Department of Biological Chemistry and in the neuroscience department, investigates the formation of lasting memories. She focuses on growth factors in the hippocampus that turn on or off the particular genes involved in the growth of neurons and in establishing memories. Levels of these growth factors elevate during activity in the normal brain, and mice with lower-than-usual levels perform poorly on spatial memory tests such as navigating mazes. In addiction studies, researchers showed chronic drug use causes the release of brain-derived growth factors in rat brain areas involved in sensing the drug-associated “reward.” Meffert’s group studies how the brain-derived growth factors turn genes on or off to control long-lasting brain responses, such as those occurring in learning and memory, or addiction. By investigating the regulation of these genes in healthy and diseased neurons, the Meffert lab uncovered the mechanism by which brain-derived growth factors rapidly and specifically alter these genes. These findings may one day help us understand and develop therapeutic targets for failures in memory and brain processing as they pertain to addiction.