Drug that Thwarts Nicotine Addiction May Help with Alcohol Dependence

July 10, 2007

SAN FRANCISCO -- A drug already approved as a smoking-cessation aid might also have a role in the treatment of alcohol dependence, if results achieved in animals carry over to humans.

SAN FRANCISCO, July 10 -- A drug already approved as a smoking-cessation aid might also have role in the treatment of alcohol dependence, if results achieved in animals carry over to humans.

A single dose of varenicline (Chantix) reduced alcohol consumption by 50% in rats, investigators here reported in the July 9 issue of Proceedings of the National Academy of Sciences. The reduction was maintained during six days of treatment.

The animals' seeking behavior toward a sugar water solution did not change during varenicline treatment, suggesting no adverse effects on appetite, said Selena Bartlett, Ph.D., of the University of California, San Francisco, and colleagues.

Importantly, the researchers noted, discontinuation of varenicline did not lead to a rebound effect on alcohol consumption, which returned to baseline levels prior to development of dependence.

Only three medications are available in the U.S. for treatment of alcohol dependence: disulfiram, acamprosate, and naltrexone. Of those, the opioid antagonist naltrexone has demonstrated the most consistent effect, the authors noted. However, some patients do not respond to naltrexone and opioid receptor antagonists decrease consumption of sucrose, as well as ethanol, in rats.

Some evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine addiction, supported by the common co-occurrence of alcohol and nicotine dependence.

Nicotine binds directly to the receptor, while alcohol induces the release of another neurotransmitter, acetylcholine, which then activates the receptor. Either way, dopamine is released.

Varenicline is a partial agonist at the ?4?2 nAChR and is approved as a smoking-cessation aid in the U.S. and more than 30 other countries. To evaluate the drug's potential for treatment of alcohol dependence, Dr. Bartlett and colleagues evaluated its effect in a model of drinking and reward-seeking in rats.

After a training period consisting of about 5 months of alcohol exposure, rats received varenicline at a dose of 0.3, 1, or 2 mg/kg 30 minutes before a study session.

The drug significantly inhibited the animals' self-administration of a 10% alcohol solution (P