Effectiveness of addiction drugs 'depends on phase of addiction'
The notion that "one size fits all" when applying drug treatments to addiction is challenged by a new study published in the journal Biological Psychiatry that investigates pharmacotherapies for cocaine addiction.
Currently, medication for drug addicts is prescribed in the same way for all patients, regardless of the extent of their addiction. The new study uses cocaine addiction - for which there are currently no Food and Drug Administration (FDA)-approved drug therapies - to study whether treatment is more or less responsive at different stages of addiction.
Increasingly, evidence suggests that addiction is caused by a convergence of different "neurobiological adaptations" that result in an eventual loss of control over drug-seeking behaviors. Cocaine, for instance, impairs the processes that govern impulse control but also promotes drug-seeking habits.
The adaptations within the brain triggered by addictive drugs include reduced metabolic activity and reduced production of dopamine - the hormone that controls the brain's reward and pleasure centers.
At some point, over the course of addiction, a brain region called the nucleus accumbens takes over from the dorsolateral striatum (DLS) in managing control behaviors - systems that are both involved in the production of dopamine. As the nucleus accumbens is responsible for processing reward and the DLS is involved in habits, this shift results in a behavior change that favors high impulsivity and compulsive drug seeking.
How do impulsivity and the brain's dopamine systems interact in addiction?
To study how the DLS, impulsivity and phase of addiction of a subject influence their responsiveness to drug interventions, the researchers behind the new study - from the University of Cambridge in the UK - conducted an experiment in an animal model.
The rats that were in an early phase of addiction were not affected by the treatment. Instead, it was the animals who had a longer history of self-administering cocaine that exhibited the greatest change in behavior.
First, the "impulsivity" of 40 male rats was measured using a task in which rats were trained to self-administer food pellets by pushing open a panel during allocated periods signaled to the rats using a light.
Next, these rats were trained to press a lever to self-administer cocaine dissolved in water. The extent to which the rats exhibited cocaine-seeking behavior - for instance, repeatedly pressing the lever, even when cocaine was not delivered - was monitored by the researchers.
The team then administered a dopamine receptor-blocking drug called α-flupenthixol directly into the DLS of rats at various phases of addiction.
The researchers found that, after receiving the drug, most rats reduced their cocaine-seeking behavior, but that the extent of this behavior change was also influenced by the inherent impulsivity of the rats. The highly-impulsive rats were not as affected by the drug as the rats who scored as being "low impulsive."
Also, the rats that were in an early phase of addiction were not affected by the treatment. Instead, it was the animals that had a longer history of self-administering cocaine that exhibited the greatest change in behavior.
Dr. John Krystal, editor of Biological Psychiatry, says the results show that dopamine receptor blockers play a role in treatment of addiction, but only at particular phases of the addiction process.
"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," he says.
"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," adds first author Dr. Jennifer Murray.
"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."
In 2013, Medical News Today reported on a study from Connecticut College that suggested laboratory rats find Oreo cookies to be "as addictive as cocaine."
Written by David McNamee
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