How the Molecule CREB Helps Explain Addictive Behavior

Molecule CREB

Decades ago, addiction was viewed as a personal weakness or failing. As our understanding of the body and brain has progressed, however, we now realize that drug addiction is a complicated disease. Scientists continue to study addiction on numerous levels: drug-seeking behavior, cravings, brain areas associated with addiction, and societal factors that perpetuate substance abuse.Other researchers are peering into cells themselves to understand addiction at a molecular level. Their findings may alter how we conceptualize and treat the disease of drug addiction.

The Role of CREB in Healthy Individuals

the role of the crebCyclic AMP response element-binding protein, or CREB, is a molecule produced in cells throughout the body. CREB modulates the process whereby DNA, the genetic code of the cell, is expressed. Thus, changing the levels of CREB in a cell can affect which genes are turned on and off.

CREB controls the transcription, or expression, of a variety of genes. The most prominent genes include brain derived neurotrophic factor, enkephalin, and tyrosine hydroxylase. In brain cells, CREB is particularly important in memory circuits.For example, formation of long-term memories depends on the activity of CREB in neurons. In particular, the molecule causes long lasting changes in neurons that make them more likely to fire together in the future. Thus, CREB activity leads to stronger brain circuits associated with learning and memory.

How Can CREB Affect the Course of Addiction?

Although the thoughts and behaviors associated with addiction are complicated, drug-seeking behaviors are one of the core problems. The first time your loved one took a drug, brain regions associated with reward became active. With repeated experiences with the drug, these circuits become stronger and stronger.The key network associated with addiction involves the limbic system, with a structure called the nucleus accumbens being particularly changed by drug use.

Manipulating CREB Levels

manipulating creb levelsSeveral classes of drugs, including opiates, cocaine, and amphetamine, lead to CREB activity within the nucleus accumbens. Many of the studies have been performed in animals, because it is easier to manipulate CREB levels in rodents than in humans. Much of the research in this area shows that increased CREB is associated with lower sensitivity to reward. This explains why people who abuse drugs develop tolerance to the substance. Eventually, they require more and more of the drug to get the same level of response.

Additionally, increased CREB in the nucleus accumbens may trigger negative emotional states. Thus, CREB may be one molecule underlying the increased risk for depression observed among people struggling with addiction.

How Does Our Knowledge of CREB Affect Treatment?

Unfortunately, scientific research has not yet found a way to change CREB levels in humans. However, it is possible that this is a future therapeutic target for people with substance abuse. Finding a way to turn off the effects of CREB in the nucleus accumbens may reset the brain’s reward pathway. This could be used to break the associations between drugs and reward in a person’s brain, reducing the likelihood that they will engage in drug-seeking behaviors.

Although our ability to directly manipulate CREB is currently limited, this is not to say that existing treatments cannot impact CREB pathways. Medications and psychotherapeutic approaches may modify pathways involving the nucleus accumbens.This may cause a change in CREB, facilitating successful recovery in people receiving professional treatment for drug addiction. Future research about CREB and related molecules may further hone our ability to treat addiction on a molecular level.

  1. McPherson, C.S. & Lawrence, A.J. (2007). The nuclear transcription factor CREB: involvement in addiction, deletion models, and looking forward. Current Neuropharmacology, 5(3): 202-212.

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