03 Sep Study Explores Window of Opportunity for Meds in Substance Treatment
People affected by substance addiction experience lasting changes in the production of a pleasure-producing brain chemical called dopamine. However, the areas of the brain primarily impacted by these changes shift over time. In a study published in July 2014 in the journal Biological Psychiatry, a team of French and British researchers used laboratory experiments on rats to explore the relative effectiveness of substance treatment medications in different stages of addiction-related brain alteration. These researchers concluded that the effects of a medication can vary significantly when used at specific points in the addiction process.
The vast majority of the substances targeted for abuse produce a powerful sensation called euphoria by increasing the amount of dopamine circulating in the brain’s pleasure center. As a rule, the amount of euphoria triggered by substance use is much higher than the pleasure associated with such everyday activities as eating tasty foods, having sex or engaging in favored hobbies. In practical terms, this means that some people who start using drugs or alcohol will continue their intake as part of an effort to re-experience their original euphoric feelings. With repeated exposure, the temporary spikes in dopamine levels can lead to long-term changes in brain function and the establishment of physical dependence. In turn, a physically dependent substance user typically has drastically elevated risks for developing the damaging symptoms of substance addiction. In fact, addiction follows dependence so frequently that experts in the field sometimes use both terms interchangeably for the same basic brain conditions.
Shifting Brain Areas
Two brain areas are heavily affected by changes in dopamine levels. In the earlier stages of addiction, the main impacted area helps the brain gauge the amount of reward triggered by feelings of euphoria. However, as addiction advances, the main impact shifts to a second brain area that normally helps a person control his or her behavior. The shift between the two areas is characterized by a decrease in the voluntary use of a substance as a source of pleasure and an increase in the involuntary use of a substance as part of a pattern of impulsive behavior. After undergoing this switchover, a substance user has a much greater chance of displaying one of the hallmarks of entrenched addiction: compulsive substance use that fails to yield to a person’s efforts to rein in his or her intake.
Effectiveness of Substance Treatment Medication
In the study published in Biological Psychiatry, researchers from the University of Aix-Marseilles, the University of Cambridge and five other French and British institutions used laboratory experiments on rats to explore the brain reactions to substance treatment medication during various stages of the addiction process. The specific medication under consideration, called alpha-flupenthixol, is a proposed treatment for cocaine addiction, a condition that currently has no verified medication option. Some of the rats involved in the experiments were in relatively early stages of addiction and did not display elevated levels of impulsive behavior. Other rats were further along in the addiction process and did display elevated impulsivity levels.
After being trained to administer cocaine to themselves, all of the rats received doses of the anti-addiction medication. Most of these rats subsequently reduced the amount of cocaine they consumed; however, not all rats responded to medication equally well. As a rule, the rats with heightened levels of impulsive behavior had smaller chances of substantially reducing their cocaine intake, while the rats with relatively low levels of impulsive behavior had greater chances of curbing their cocaine use. The researchers used these findings as the basis for two conclusions. First, a high level of impulsivity can potentially make a substance treatment medication less effective in an individual. In addition, since impulsivity is linked with the brain changes produced by advancing addiction, people heavily affected by addiction may not respond to substance treatment medications as well as people in earlier stages of the addiction process.
Interestingly, the study’s authors also concluded that the rats in the earliest stages of cocaine addiction did not respond well to treatment with the medication. This finding suggests that substance treatment medications may have a window of effectiveness that first opens up when an individual has advanced at least somewhat down the path of addiction-related brain change. Finally, the authors concluded that highly impulsive people are probably susceptible to addiction because they can’t reestablish control over their substance-using behaviors, not because they seek out substances in the first place.
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