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Scientists unravel brain circuits involved in substance cravings

Posted on 03-07-16 in Addiction, Recovery

Scientists unravel brain circuits involved in substance cravings

One of the most difficult tasks in addiction treatment and recovery is dealing with powerful cravings or urges to use alcohol or drugs. Although cravings are short-lived, they are a major contributing factor to an individual’s propensity for relapse following a period of abstinence.

Intense alcohol or drug cravings are associated with reward and motivation in certain areas of the brain, including the nucleus accumbens in the ventral striatum and the medial prefrontal cortex. The release of dopamine in the ventral striatum, for example, plays a significant role in reinforcing drug use. Shelly B. Flagel and her colleagues found that dopamine acts selectively in a form of stimulus-reward learning, which assigns incentive salience (“wanting”) to rewards and serves as a powerful behavior motivator.

Scientists often use Pavlov’s classical conditioning approach to explain the behavioral motivation to use drugs. Cravings can result from the repeated pairing of certain environmental or external cues (e.g., people, places, sounds, smells, certain emotional states) with drug use and other addictive behaviors (e.g., gambling, sex, food). Those in recovery for drug addiction may feel more motivated to use alcohol or drugs when they are presented with these external cues or triggers, even when the drug is not present, according to Barbara Ramos, Ph.D., a research associate at McMaster University.

With the repeated pairing of a cue with a reward, the motivation to seek and obtain the reward can be transferred from the reward to the cue itself. When the cue is presented without the reward, the motivation to seek and obtain the reward will remain intact. This is because the incentive salience, or “want” to use a drug, has been transferred to the cue itself. This process explains why people presented with certain triggers (i.e., certain people, places, smells, sounds, etc.) can be motivated to use drugs despite a period of abstinence. A new study provides a novel approach for reducing or eliminating substance abuse cravings. By disrupting the activity in the ventral pallidum, an area of the brain involved in behavioral motivation and reward, the transfer of incentive value of cues paired with reward can be prevented, and strong cravings that motivate a person to seek and obtain a drug may be suppressed, according to the new study published in the European Journal of Neuroscience.

The incentive sensitization theory

Incentive salience depends on a person’s current neurobiological state, reward motivation and previously learned associations about a reward. The incentive sensitization theory suggests that incentive salience is a relatively unconscious process that involves highly sensitized neural systems such as the mesocorticolimbic brain system, said Kent C. Berridge, Ph.D., professor of psychology and neuroscience at the University of Michigan.

The pairing of an external stimulus cue with drug use primes a person’s motivation to obtain and consume more of the reward (i.e., drug); this “wanting” is further amplified by certain neurobiological and physiological states and other brain changes induced by repeated drug use. Stress states, for example, can amplify the conditioned response for a reward and the level of “wanting” for the drug the moment an individual re-encounters a cue by elevating signals to release dopamine in the mesocorticolimbic system.

Incentive salience theory explains how someone can irrationally “want” a drug, but not “like” or have a desire to use a drug. This “wanting” can motivate people to pursue and consume a reward, even if they know that they will not like it, Berridge said.

Incentive salience and cravings

The ventral pallidum is a brain region involved in a number of conditioned and unconditioned reward-seeking behaviors. The ventral pallidum attributes value to cues paired with rewards, according to Stephen E. Chang, Ph.D., and his colleagues. The researchers used a new technology called designer receptors exclusively activated by designer drugs (DREADDs) to repeatedly disrupt ventral pallidum activity in rats.

Some rats (sign-trackers) attribute strong incentive salience to a conditioned stimulus cue (i.e., metal lever inserted into a chamber) that predicts reward (i.e., food). Sign-trackers are more likely to approach the metal lever and eagerly sniff and nibble at it whenever it appears due to its association with food (i.e., reward). Following the inactivation of the ventral pallidum, the researchers inserted a lever into the experimental chamber for 10 seconds, followed by a food pellet reward when the lever was withdrawn. Food was given to the rats regardless of the behavior, but the sign-tracker rats pressed the lever and bit the lever as if it were the reward itself.

The researchers demonstrated that by injecting clozapine N-oxide (CNO) into the ventral pallidum, they were able to suppress the activity of the ventral pallidum and block the rats’ sign-tracking behavior (i.e., pressing the lever). The researchers concluded that the inactivation of the ventral pallidum during “sign-tracking” disrupted the transfer of incentive value to obtain the reward. This new study provides evidence for the role of the ventral pallidum in the motivational behaviors underlying drug addiction. Targeting the ventral pallidum may be useful for taking away the incentive to use drugs in response to triggers among people with drug addiction.

The incentive to use drugs is problematic for many people in alcohol and drug abuse recovery, leading to high rates of relapse. People in recovery face triggers that can motivate them to use even after they have achieved long periods of sobriety. The Sovereign Health Group understands the importance of identifying and managing triggers and drug cravings in treatment and recovery for individuals with drug and alcohol addiction. Our evidence-based treatment programs for eating disorders, substance abuse, mental illness and co-occurring disorders incorporate ways to recognize and deal with triggers and cravings to use drugs and alcohol. For more information on the programs offered at Sovereign Health, please contact our 24/7 helpline to speak to a member of our team.

About the author

Amanda Habermann is a writer for the Sovereign Health Group. A graduate of California Lutheran University, she received her M.S. in clinical psychology with an emphasis in psychiatric rehabilitation. She brings to the team her background in research, testing and assessment, diagnosis and recovery techniques. For more information and other inquiries about this article, contact the author at