Thursday, July 05, 2007
Researchers at the University of Maryland School of Medicine have found that cocaine exposure in rats causes permanent damage to a part of the brain responsible for judgment and learning new behaviors. The results may shed light on why drug addicts often relapse after being treated for their addiction. The study is published in the July advance online publication of the journal Nature Neuroscience.
Researchers tested whether rats that had been exposed to cocaine for several weeks could learn to distinguish between two different odor cues – one that gave them water laced with sucrose and the other which was water laced with bitter tasting quinine. "We then reversed the two odor cues, so the odor predictive of the sugar reward became predictive of quinine and vice versa. In earlier experiments, normal rats have been able to learn this new association," says Geoffrey Schoenbaum, M.D., Ph.D., an assistant professor of anatomy and neurobiology at the University of Maryland School of Medicine and lead researcher on the study. "We found that rats exposed to cocaine were much slower than non-drug exposed rats at changing their behavior after the reversal."
Similar deficits previously have been shown in human cocaine addicts and are thought to reflect the poor decision-making that is characteristic of addiction. The researchers found that this deficit was associated with declines in flexible signaling in the part of the brain called the basolateral amygdala, located deep in the temporal lobe. Rather than being able to process new information, as in normal animals, electrical signaling in the basolateral amygdala continued to provide the old odor association for reward and punishment in the cocaine-treated rats.
"The drug-exposed rats couldn’t change their behavior because neurons in the amygdala were essentially still signaling what they learned before reversal," says Dr. Schoenbaum. "Flexible signaling in the amygdala is compromised by previous exposure to drugs."
A second experiment confirmed that the deficit was fixed when the researchers destroyed the basolateral amygdala. "Remarkably, lesions that destroyed these neurons fixed the reversal deficit," says Dr. Schoenbaum. "The drug-exposed rats with lesions in the amygdala performed as well on reversals as rats that were never exposed to cocaine."
"It’s clear that exposing rats to cocaine can cause fundamental deficits in adaptive decision-making," says Dr. Schoenbaum. "These results are important in understanding how addictive drugs change the brain and also provide information that may lead to potential therapeutics agents for the treatment of addiction."
Funding for Dr. Schoenbaum’s research was provided by the National Institute on Drug Abuse.