Compounds that target a certain opioid receptor in the brain could be used to develop a new group of antidepressants, researchers reported in a study published in the journal Neuropsychopharmacology in September.

New treatments for depression could benefit patients who don’t respond to existing treatments, which are most commonly SSRI-class antidepressants (Prozac, Paxil, Lexapro, etc.) that act on the serotonin system in the brain.

In the new study, the researchers investigated tianeptine, a medication used to treat depression and anxiety in several countries, but whose mechanism of action was not known.

The team injected mice with tianeptine and then conducted a series of standard behavioral tests designed to pick up depression-like behaviors in the animals and measure the effects of drugs.

The results showed that tianeptine has an antidepressant effect, which they trace to its action on a class of receptors on brain cells called the mu opioid receptor (MOR). Tianeptine did not work on mice that lacked the MOR receptor.

MOR is the same receptor that’s targeted by classic opioid drugs such as morphine. Tianeptine also had a morphine-like effect on the animals’ food intake and pain sensitivity. But unlike morphine, tianeptine did not appear to be addictive, in these animal tests. Mice that received tianeptine for 30 days did not become tolerant to the drug and didn’t show withdrawal effects.

The findings suggest it may be possible to target the MOR system in specific ways to produce antidepressant effects without the side effects of opioid drugs. More studies will be required to determine whether tianeptine or other MOR modulators are effective in subsets of depressed patients, the researchers said.

The team was led by René Hen, Ph.D., of Columbia University, a Foundation Scientific Council Member, 2009 and 2003 Distinguished Investigator, and 1998 Independent Investigator. The team also included Benjamin A. Samuels, Ph.D., of Rutgers, a Young Investigator in 2014 and 2012; Katherine M. Nautiyal, Ph.D. of Columbia University, a 2015 NARSAD Young Investigator; and Jonathan A. Javitch, M.D., Ph.D. of Columbia University, a Foundation Scientific Council Member, 2010 Distinguished Investigator, 2003 Independent Investigator, and a 1992 and 1990 Young Investigator.