Addiction Silences Synapses in Reward Circuits

Reports new study in Biological Psychiatry

Philadelphia, PA, August 2, 2016

In addiction, cues in the environment can form strong associations with the drug of abuse. A new study in Biological Psychiatry suggests that alterations in silent synapses, inactive connections between neurons, could be the neural mechanism underlying the formation of these drug-related memories. The alterations were found in the nucleus accumbens, a brain region involved in reward-related learning.

“The persistence and inflexibility of addiction-related associations are factors that trigger craving and relapse,” said Dr. John Krystal, Editor of Biological Psychiatry. “This study suggests that one factor that may contribute to this inflexibility is that synapses in reward circuits that might promote recovery are silenced,” he said, adding that with better understanding of this phenomenon, engaging these silent synapses during treatment may be an important component of recovery.

Long-term memories likely form when selective alterations in synaptic connections occur within patterns of neurons called neuronal ensembles. In the study, Bruce Hope, from the National Institutes of Health National Institute on Drug Abuse Intramural Research Program in Baltimore, Maryland, and colleagues used animal models to investigate if the brain forms drug-related memories in a similar way.

The researchers administered cocaine injections to mice, always in the same environment. After repeated injections, the mice developed an association between the drug and the environment, which produced a learned behavior when the mice were returned to the same location.

To determine how the brain encodes this drug-related behavior, the researchers need to know exactly which neurons are involved. This seemingly impossible task led most previous studies to examine randomly selected neurons or focus on a specific type of cell. In this study, the researchers used a marker that caused neurons to fluoresce when activated, allowing them to pinpoint specific neuronal ensembles involved in the behavior.

The researchers measured electrical activity of the neurons within the ensemble and compared it with nearby neurons that were not activated by the environmental cue. They found an increase in silent synapses on only the activated neurons, indicating the synaptic alterations were specific to the neuronal ensemble that encoded the drug-related memory. According to Hope, “These ensemble-specific silent synapses may be one of the mechanisms by which neuronal ensembles are modified to store memories.”

Identification of the alterations responsible for drug-related memories could open the door to treatment options for people with addiction. “Therapeutic targeting of such alterations on only this small percentage of drug memory-specific neurons could be a highly specific method for disrupting drug-related memories that mediate human addiction,” said Hope.


Notes for editors
The article is "Associative Learning Drives the Formation of Silent Synapses in Neuronal Ensembles of the Nucleus Accumbens," by Leslie R. Whitaker, Paulo E. Carneiro de Oliveira, Kylie B. McPherson, Rebecca V. Fallon, Cleopatra S. Planeta, Antonello Bonci, and Bruce T. Hope (doi: 10.1016/j.biopsych.2015.08.006). It appears in Biological Psychiatry, volume 80, issue 3 (2016), published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at +1 214 648 0880 or Journalists wishing to interview the authors may contact Bruce Hope at

The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 140 Psychiatry titles and 11th out of 256 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2015 Impact Factor score for Biological Psychiatry is 11.212.

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Media contact
Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880