Cocaine addiction: Phase-specific biology and treatment?

New findings from a study in Biological Psychiatry

2014-06-30

(Press-News.org) Philadelphia, PA, June 30, 2014 – Current pharmacotherapies for addiction follow the dictum "one size fits all". Medications are prescribed in the same way for all patients, regardless of whether they have just started experimenting with a drug or have an established drug habit. Even more troubling, there are no FDA-approved pharmacotherapies for some addictions, such as compulsive cocaine use.

Perhaps testing drugs in ways that focus on particular phases of addiction or particular clinical features of addiction, such as a patient's level of impulsivity, might advance the development of drug treatments for cocaine addiction.

Addiction is characterized by a transition from strategic drug-seeking (i.e., where a decision is made to try a drug to generate a desired effect) to habitual drug-seeking (i.e., where the behavior is triggered by the availability of drugs, particularly in contexts associated with drug use). Habitual drug use is less dependent than strategic use on whether the person actually enjoys the effects of the drug or whether there are negative subjective effects or problems associated with taking the substance.

The transition from strategic to habitual drug-seeking is associated with changes in the brain, where dopamine systems are involved in shifting the representation of drug-taking in the striatum region of the brain from the lower (ventral) part of the striatum, implicated in reward, to the higher (dorsolateral) striatum, implicated in habits.

Researchers now have identified the stages of this process that are sensitive to blockade of dopamine receptors, potential therapeutic targets, and the important role that impulsivity plays in this process. They report their results in the current issue of Biological Psychiatry.

They administered a dopamine receptor-blocking drug, α-flupenthixol, directly into the dorsolateral striatum of rats at different phases of addiction. They found that the rats transitioned from insensitivity to sensitivity to the drug's inhibitory effects on cocaine-seeking, but that this transition was also influenced by the inherent impulsivity of the rats.

Early in the addiction process, all rodents were insensitive to the drug's effects, but it did suppress drug-seeking in animals with long-standing cocaine self-administration. They also found that highly impulsive animals made the transition from drug insensitivity to sensitivity more slowly than animals with low levels of impulsivity.

"The results of this study are important because they show that although both impulsive and non-impulsive rats developed cocaine-seeking habits, this was delayed in high impulsive rats," said first author Dr. Jennifer Murray, from University of Cambridge.

These data suggest that impulsivity does not simply promote compulsivity through the facilitation of habits, but rather that these are interacting independent processes.

Murray added, "It is suggested that vulnerability to addiction conferred by impulsivity is less influenced by the propensity to develop drug-seeking habits and more by the inability of an individual to regain control over these habits that are rigidly and maladaptively established in the brain."

"The notion that particular brain mechanisms are engaged only at particular phases of the addiction process strikes me as an important insight that has yet to be harnessed in developing new medications for addiction treatment," said Dr. John Krystal, Editor of Biological Psychiatry. "This study highlights that dopamine receptor blockers might play a role, but only at particular phases of the addiction process."

INFORMATION: The article is "Increased Impulsivity Retards the Transition to Dorsolateral Striatal Dopamine Control of Cocaine Seeking" by Jennifer E. Murray, Ruth Dilleen, Yann Pelloux, Daina Economidou, Jeffrey W. Dalley, David Belin, and Barry J. Everitt (doi: 10.1016/j.biopsych.2013.09.011). The article appears in Biological Psychiatry, Volume 76, Issue 1 (July 1, 2014), published by Elsevier.

Notes for editors Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Jennifer Murray at +44 (0) 1223 765285 or jem98@cam.ac.uk.

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 4th out of 135 Psychiatry titles and 13th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2012 Impact Factor score for Biological Psychiatry is 9.247.

About Elsevier Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey — and publishes nearly 2,200 journals, including The Lancet and Cell, and over 25,000 book titles, including a number of iconic reference works.

The company is part of Reed Elsevier Group PLC, a world-leading provider of professional information solutions in the Science, Medical, Legal and Risk and Business sectors, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Media contact Rhiannon Bugno
Editorial Office Biological Psychiatry
+1 214 648 0880
Biol.Psych@utsouthwestern.edu

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Cocaine addiction: Phase-specific biology and treatment?

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