- A substantial number of people who undergo treatment for alcoholism will relapse.
- A compilation of rodent studies has found numerous reasons for alcohol relapse.
- Alcohol deprivation, stress and environmental cues can all promote relapse drinking.
- Genetic susceptibility and neuronal changes produced by chronic drinking also contribute.
What is colloquially and sometimes humorously referred to as "falling off the wagon" is, in fact, a serious problem for individuals who have undergone treatment for alcohol abuse or alcoholism. Alcohol relapse, with an emphasis on its underlying behavioral and neurobiological causes, was the focus of a workshop given during the June 2000 Research Society on Alcoholism meeting in Denver. The workshop proceedings are published in the February issue of Alcoholism: Clinical & Experimental Research.
William J. McBride, professor of neurobiology at the Indiana University School of Medicine and lead author of the workshop compilation, noted four key findings. "First," he said, "chronic alcohol drinking produces long-lasting effects in the brain that persist in the absence of alcohol and promote alcohol relapse drinking. Some of these long-lasting alterations occur within the dopamine and serotonin systems that are known to regulate alcohol drinking. Third, brain systems that promote relapse drinking are triggered by stress and cues previously associated with alcohol drinking. Fourth, individuals with a genetic background of susceptibility to high alcohol drinking are more likely to relapse."
Workshop data were gathered from several different studies of alcohol relapse using rodent models. One study introduced prolonged alcohol consumption, followed by repeated periods of alcohol deprivation, to test for an alcohol deprivation effect (ADE). ADE is similar to the binge drinking that can occur after a long period of abstinence. Another study used operant techniques such as lever pressing to examine how hard rodents would work for their alcohol following deprivation. Another assessed the impact of environmental cues and stress on the reinstatement of alcohol response. An additional study tested the effectiveness of acamprosate and naltrexone, two medications currently used to treat alcoholics. Yet one more study used microdialysis and [14C]-2-deoxyglucose techniques to examine neuronal alterations associated with alcohol relapse.
"Obviously we cannot give rodents a questionnaire to get a self report on their craving," said David Overstreet, associate professor of psychiatry with the Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill. "Instead, we look at the ADE, or how much they drink following deprivation."
Prolonged free-choice alcohol consumption, followed by alcohol deprivation, produced a significant ADE. Scientists also observed a loss of control following alcohol reinstatement. Following repeated alcohol deprivation, rodents developed a preference for higher concentrations of alcohol, which in turn, produced an increase in the magnitude and duration of the ADE. Both acamprosate and naltrexone effectively reduced the ADE in some of the rodents.
"The assumption is that rats that drink more must have had a higher craving for alcohol," said Overstreet. "Since craving is regarded as a key contributor to relapse in humans, medications that work on blocking increased drinking that may follow alcohol deprivation might be clinically useful." Overstreet noted that a substantial number of people who have gone through treatment will relapse to heavy drinking. "Understanding the factors that promote relapse in animal models will help us combat relapse in humans by devising better behavioral and pharmacological treatments," he said.
Factors such as stress and exposure to situations previously associated with alcohol drinking (referred to as "cues") were also found to contribute to relapse drinking.
"Knowing that environmental cues can foster relapse," said Overstreet, "may lead to the development of 'desensitization programs' for humans, where recovering alcoholics are exposed to suspected 'triggers' while under supportive care. The idea behind this type of treatment is that the cues - such as those associated with a bar - will, eventually, not have the same impact on the individual." Regardless what direction future treatments may take, Overstreet noted that the workshop proceedings had made an important contribution to the field by having "verified that the medicines approved for the treatment of alcoholics work, and confirmed what was suspected, that stress and environmental cues can influence relapse."
The third major area of findings involved changes in brain activity following alcohol exposure. When chronic drinking followed a prolonged period of deprivation, scientists found evidence of long-lasting alterations in neuronal activity, serotonin receptor function, and dopamine neurotransmission within the mesolimbic system.
"These results show that chronic alcohol drinking produces changes in several different neural systems," said McBride. "Some of these changes persist in the absence of alcohol, resulting in imbalances in neuronal systems within the brain. These imbalances within the brain make the individual more vulnerable to relapse alcohol drinking."
McBride added that it is important to look at the large number of factors that influence alcohol relapse "in order to effectively evaluate the impact that genetics, stress and environmental cues have on relapse drinking, and on the neuronal alterations which underlie relapse drinking. All of this information," he said, "can greatly aid in the development of pharmacotherapies for the treatment of alcohol relapse."
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Dzung-Anh Le of the Biobehavioral Research Department at the Addiction Research Foundation in Toronto, Ontario; and Antonio Noronha of the National Institute on Alcohol Abuse and Alcoholism.