A drug prescribed for male and female infertility and menstrual disorders could hold the key to a more effective treatment for alcoholism, according to a study by researchers at the UCSF-affiliated Ernest Gallo Clinic and Research Center.
The study showed that "alcoholic" rodents, when injected with the drug cabergoline, decreased their alcohol consumption and alcohol-seeking behavior and were less likely to relapse.
Cabergoline, which is marketed under the trade name Dostinex, is approved by the Food and Drug Administration in pill form to treat conditions caused by excess of the hormone prolactin.
The study, led by Dorit Ron, PhD, a principal investigator at the Gallo Center and associate professor of neurology at UCSF, is now on line (February 20, 2009), in the journal "Biological Psychiatry."
Notably, cabergoline did not impact the rats' consumption of sucrose and, in a subgroup of binge-drinking mice, the drug did not appear to significantly affect intake of water or saccharin.
"This is encouraging," says Ron, "because it demonstrates that cabergoline is specific for alcohol, but does not affect general reward or pleasure. One of the problems with some existing drugs to treat alcoholism is a side effect that decreases pleasure, making compliance an obstacle to sobriety."
The research builds on an earlier, provocative finding by Ron and her colleagues regarding the protein GDNF (glial cell line-derived neurotrophic factor), which they had injected into rats' VTA (ventral tegmental area) brain region, associated with drug-seeking behavior.
In this earlier study, the scientists had trained rats to consume alcohol. Some, like humans, drank in moderation, while others binged. But when GDNF was administered, both heavy and light drinkers lost at least some of their craving for alcohol. This effect became apparent within 10 minutes and lasted at least 24 hours, the scientists discovered. Importantly, administration of GDNF into the brain prevented the rats from relapsing after a period of abstinence.
While the discovery broke new ground, the scientists knew that GDNF could not be used to treat alcoholic humans because its molecule is too large to cross the blood-brain barrier. So, in the present study, Ron and her colleagues looked at cabergoline, a compound that has been shown in cells to increase the expression of GDNF.
After establishing that cabergoline treatment resulted in an increase of the level of GDNF and activation of the GDNF pathway in the rats' VTA, the researchers sought to test its impact on rodents' drinking habits.
Rats underwent a two-month training program in which they learned to press a lever to obtain alcohol. Researchers found that when rats were injected with cabergoline, they were less likely to press the lever. The higher the dose of cabergoline, the lower the number of lever presses reported. The researchers also found that binge-drinking mice consumed less alcohol after cabergoline administration.