In Mice, Ketamine Reverses Depressive-like Behavior after Alcohol Abstinence

In Mice, Ketamine Reverses Depressive-like Behavior after Alcohol Abstinence

Posted: April 22, 2016

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Takeaway: Alcoholism and depression often occur together. A new study in mice suggests the experimental drug ketamine could be helpful in treating depressive symptoms after alcohol withdrawal.

The drug ketamine may be useful in reversing some of the depressive-like behavior seen in rodents after an extended period of alcohol abstinence, according a study published February 10, 2016 in the journal Neuropsychopharmacology. Although alcoholism and depression are often found together in patients, there are few treatments that address both illnesses. Until now, ketamine has been tested mostly as an experimental antidepressant in patients with treatment-resistant depression and bipolar disorder.

The study’s researchers include Vanderbilt University team leader Danny G. Winder, Ph.D., a 2002 Young Investigator and a 2013 Distinguished Investigator, and Sachin Patel, M.D., Ph.D., a 2015 Independent Investigator also at Vanderbilt. They looked at changes in the behavior of female mice that drank from bottles containing 10 percent ethyl alcohol for six weeks, and then had their drinking mixture replaced with just water. In this abstinent condition, the mice developed depressive-like behaviors in two experiments: a forced swim test, and a novelty-suppressed feeding test where hungry mice are offered food in a new environment. (Mice that remain immobile in the swim test or avoid the food in the feeding test are behaving in ways that are thought to correspond to depressive and anxious behaviors in humans.)

These depressive-like behaviors did not appear directly after alcohol was removed from the drinking bottles, but instead took up to two weeks’ of abstinence to appear, the scientists found. Moreover, the depressive-like behavior continued even after 35 days of alcohol withdrawal. However, a dose of either ketamine or another experimental drug called JZL-184, reversed the depressive behaviors produced by abstinence.

The study also confirmed that mice previously exposed to the 10 percent alcohol mix for 42 days would prefer a lower concentration (3 percent alcohol) over plain water, compared to mice that had never been exposed to an alcohol-water mix. These findings, say the scientists, suggest that alcohol preference in these mice is possibly habit-driven. With the promising results found with ketamine and JZL-184, the researchers suggest their study may offer insights into developing new treatments for alcohol-withdrawal mood and anxiety disorders.