Relapse

A recent NIDA study builds upon previous research findings into the relationship between stress and drug abuse, by identifying a direct link between stress- and reward-associated mechanisms in the brains of rats.

Dr. Roy Wise, of the National Institute on Drug Abuse, and colleagues from Tufts University and the University of Pennsylvania School of Medicine examined the effects of stress in adult male rats exposed to cocaine. The rats were trained to self-administer cocaine or saline (controls) and then subjected to withdrawal. Following training and withdrawal, the rats were exposed to a series of footshocks. The scientists then tested for the presence of stress-related chemicals in the brains of cocaine-exposed and control rats.

Researchers found that both cocaine-exposed and control rats had increased levels of the stress-related compound corticotropin-releasing factor (CRF) in the ventral tegmental area (VTA), a region of the brain associated with pleasure. Moreover, the presence of stress compound in the VTA was found to trigger a relapse to drug-seeking behavior by the cocaine-exposed rats.

What it means:These findings establish the VTA as the stress-associated release site for CRF. The presence of CRF in the brain activates reward systems—initiating relapse to drug-seeking behavior in cocaine-experienced rats—and highlights a link between stress mechanisms and drug reward pathways.

The scientists published their findings in the June 1, 2005 issue of the Journal of Neuroscience.

NIDA NewsScan, February 1, 2006

A University of Connecticut School of Medicine researcher has found that use of quantitative electroencephalography (EEG) is a reliable tool to predict which patients with histories of abuse of alcohol,cocaine, cocaine and alcohol, or opioid dependence are prone to relapse.

EEGs were given to 107 substance-dependent patients enrolled in a treatment program and to 22 controls with no history of substance abuse. An electroencephalogram was administered when the patients had been free of alcohol or drug use for an average of 3 months. The patients were then monitored for the next 6 months to see if they resumed alcohol or drug use.

The researcher observed that the 48 patients who relapsed to substance abuse shared a similar characteristic – their EEGs showed an increased amount of high-frequency activity, compared to the 59 patients who maintained abstinence and to the 22 control subjects. This high-frequency activity on the EEGs was found to far outweigh

clinical and demographic variables as a predictor of relapse.

What it means: EEGs may prove to be a sensitive and specific screening test that can be used to identify those substance abuse patients with the highest risk for relapse. This would be an important advance for treatment planning because it would permit prevention and treatment efforts to be directed toward those at the highest risk for relapse. EEG technology is more practical and affordable than other neuroimaging technologies, including fMRI, PET, or SPECT, and it can be realistically implemented into a variety of treatment settings.

The study by Dr. Lance Bauer, Professor of Psychiatry and Director of the Neural Dynamics Laboratory at the University of Connecticut, was published in the July 2001 issue of the journal Neuropsychopharmacology.

NIDA NewsScan, October 16, 2001

Researchers from the Albert Einstein College of Medicine and NIDA’s Intramural Research Program have made a major advance in understanding the neurobiological basis for cocaine abuse relapse. It had been known previously that the learning of associations betweenenvironmental cues and taking drugs occurs in the hippocampus and that these cues are a major cause of relapse to drug-taking behavior. Now scientists have pinpointed the region (the ventral subiculum area) of the hippocampus and the neurobiological factors (glutamateneurotransmission) that may play an integral role in cocaine abuse relapse.

To arrive at these findings, the researchers first conditioned rats to obtain cocaine by pushing a lever (cocaine-seeking behavior). After this behavior had been well established, saline solution was substituted for cocaine. When the rats no longer received cocaine bypushing the lever, they greatly

decreased their lever pushing. The investigators electrically stimulated and injected pharmacological compounds into rats’ brains to regenerate cocaine-seeking behavior, and then mapped those brain areas involved in the animals’ revived interest in seeking the drug (as measured by increased lever pushing).

What it means: The findings from this study suggest that agents based on glutamate are promising candidates as potential medications for cocaine addiction, particularly in preventing environmental cue-induced relapse.

The study is published by lead investigator Dr. Stanislav R. Vorel in the May 11, 2001, issue of Science. It is available online at the journal’s Web site www.sciencemag.org.

NIDA NewsScan, May 21, 2001