Mifepristone (RU-486), an FDA-approved drug currently prescribed to terminate early pregnancy, seems to be effective in helping recovering male alcoholics avoid relapse caused by stress. This is according to a rat study by researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco.
Specifically, Mifepristone blocks the actions of progesterone and cortisol in the brain; these hormones are believed to play a role in the development of alcoholism as well as relapse.
“It’s well-known that stress can lead to relapse in people who are trying not to drink,” said senior author Selena E. Bartlett, director of medications development at the Gallo Center. “Until now, we have had very few interventions that showed potential as possible treatments.”
For the study, Bartlett and her team trained a group of male rats to press a lever in order to receive a drink from either an alcohol solution or a sucrose solution. Then the rats were conditioned to do the opposite: not to press the lever in order to get a drink— a process “sort of like rehabilitation in humans,” according to Bartlett.
After this period of forced abstinence, the rats were given yohimbine, a compound that triggers stress and relapse-like behavior in rodents.
“We wanted to see if the stressed rats would press the lever again, much as a stressed alcoholic in recovery might reach for a drink,” said Bartlett.
The rats who were given injections of mifepristone before being given yohimbine were far less likely to press the lever for a drink when compared with rats not given mifepristone.
In order to figure out exactly where the mifepristone was working in the rodents’ brains, the researchers repeated the experiment ; this time, however, before administering yohimbine, they infused mifepristone directly into the central nucleus of the amygdala, a brain region known to play a role in stress, anxiety and anxiety disorders. This brain structure plays a major role in controlling fear responses, as well as being the center of individual emotional experience.
Interestingly, in the rats trained to drink alcohol, mifepristone infusions discouraged lever-pressing behavior, but not in the rats trained to drink the sucrose solution.
“This was a very unexpected finding, but very exciting,” said Bartlett. “Identifying the area of the brain where mifepristone acts to discourage alcoholic relapse opens up the possibility of creating new compounds that are even more specific in their action.”
Currently, Bartlett and her team are working to determine which hormone mifepristone specifically blocks in discouraging relapse: cortisol or progesterone. “We are working to obtain funding to enable testing of this medication in male alcoholics,” she said.
The study is published in Neuropsychopharmacology.
Source: University of California