Cocaine addiction: Phase-specific biology and treatment?

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 , might advance the development of drug treatments for .

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, , 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 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 -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 ," 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 process."

Explore further: An advance in understanding drug 'habits' and their treatment

More 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)

Related Stories

An advance in understanding drug 'habits' and their treatment

March 26, 2014
(Medical Xpress)—Cocaine promotes habitual behaviours and these can potentially be reversed with the use of an antioxidant, research at the University of Sydney has shown.

Novel compound halts cocaine addiction and relapse behaviors

April 23, 2014
A novel compound that targets an important brain receptor has a dramatic effect against a host of cocaine addiction behaviors, including relapse behavior, a University at Buffalo animal study has found.

Addiction: Can you ever really completely leave it behind?

September 23, 2013
It is often said that once people develop an addiction, they can never completely eliminate their attraction to the abused substance. New findings provide further support for this notion by suggesting that even long-term ...

New form of brain signaling affects addiction-related behavior

June 27, 2014
University of Iowa researchers have discovered a new form of neurotransmission that influences the long-lasting memory created by addictive drugs, like cocaine and opioids, and the subsequent craving for these drugs of abuse. ...

Investigating the pleasure centers of the brain: How reward signals are transmitted

May 27, 2014
New research presented today by Dr. Jonathan Britt, from McGill University, helps to better understand how reward signals, such as those produced by addictive drugs, travel through the brain and modify brain circuits. Dr. ...

Autism-related protein shown to play vital role in addiction

May 9, 2014
In a paper published in the latest issue of the neuroscience journal Neuron, McLean Hospital investigators report that a gene essential for normal brain development, and previously linked to Autism Spectrum Disorders, also ...

Recommended for you

New surgical strategy offers hope for repairing spinal injuries

July 28, 2017
Scientists in the UK and Sweden previously developed a new surgical technique to reconnect sensory neurons to the spinal cord after traumatic spinal injuries. Now, they have gained new insight into how the technique works ...

Scientists block evolution's molecular nerve pruning in rodents

July 27, 2017
Researchers investigating why some people suffer from motor disabilities report they may have dialed back evolution's clock a few ticks by blocking molecular pruning of sophisticated brain-to-limb nerve connections in maturing ...

In witnessing the brain's 'aha!' moment, scientists shed light on biology of consciousness

July 27, 2017
Columbia scientists have identified the brain's 'aha!' moment—that flash in time when you suddenly become aware of information, such as knowing the answer to a difficult question. Today's findings in humans, combined with ...

Social influences can override aggression in male mice, study shows

July 27, 2017
Stanford University School of Medicine investigators have identified a cluster of nerve cells in the male mouse's brain that, when activated, triggers territorial rage in a variety of situations. Activating the same cluster ...

Scientists become research subjects in after-hours brain-scanning project

July 27, 2017
A quest to analyze the unique features of individual human brains evolved into the so-called Midnight Scan Club, a group of scientists who had big ideas but almost no funding and little time to research the trillions of neural ...

Researchers reveal unusual chemistry of protein with role in neurodegenerative disorders

July 27, 2017
A common feature of neurodegenerative diseases is the formation of permanent tangles of insoluble proteins in cells. The beta-amyloid plaques found in people with Alzheimer's disease and the inclusion bodies in motor neurons ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.