Investigators demonstrated in rats that repeated starting and stopping of cocaine use decreased the brain's reward function and reduced the pleasurable effects of cocaine. This decrease in pleasure-perception was highly correlated with escalation of cocaine intake.
The persistence of this pleasure deficit after stopping prolonged cocaine use may be part of the neurobiological basis for the continued craving and increased vulnerability to relapse associated with drug addiction.
The study's findings also show that tolerance does not result from a decreased effect of cocaine on basal reward thresholds, but results instead from the establishment of a new basal reward threshold, above the initial threshold. As a result, more doses are progressively needed to maintain the same hedonic effect, thereby further aggravating the dysregulation of brain reward function.
Changes in pleasure thresholds were only observed in animals that developed excessive levels of cocaine intake. Those that developed stable and moderate levels of cocaine intake did have altered pleasure perception. Thus, a chronic shift in pleasure thresholds appears to be one of the neurobiological signatures of the transition to addiction.
WHAT IT MEANS: Based on this study, it appears that promising new therapies for addiction may be based on treatments that mute the desire to escalate cocaine intake by blocking the elevation of brain reward thresholds produced by chronic cocaine use.
Serge H. Ahmed, Paul J. Kenny, and colleagues from the University of Bordeaux, France and The Scripps Research Institute in LaJolla, California published the study in the July 2002 issue of the journal Nature Neuroscience.
Materials provided by NIH/National Institute On Drug Abuse. Note: Content may be edited for style and length.
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