The drug ketamine can relieve depression within two hours and its beneficial effect on patients may last a week. But it’s also known as the party drug “Special K” and can be addictive, as well as fostering hallucinations, delusions and disorientation.
Because of the potential for misuse and addiction, “you have a novel, highly effective treatment for depression, but you can’t give it to people to take at home or on a routine basis,” said researcher Daniel Lodge, Ph.D., of the University of Texas Health Science Center at San Antonio.
Antidepressants usually take at least two weeks to show any effect in the patients they help, and not all patients benefit. If a drug were fast-acting and provided sustained relief from depression, the risk of suicide among patients would be reduced, he said.
The problem with ketamine is that the drug acts on receptors located throughout the brain, making it difficult to control its effects, he said.
Lodge and his colleagues from the Health Science Center’s Department of Pharmacology were able to identify a brain circuit involved in the beneficial effects of ketamine. The circuit sends signals between the hippocampus and the prefrontal cortex.
The researchers found that activating the circuit in rats causes antidepressant-like effects similar to those caused by ketamine, whereas preventing activation of the circuit eliminates the antidepressant-like effects of ketamine.
“The idea is, if one part of the brain contributes to the beneficial effects of ketamine, and another part contributes to its abuse and effects such as hallucinations, now we can come up with medications to target the good part and not the bad,” said Flavia R. Carreno, Ph.D., lead author of the study.
Identifying this mechanism gives scientists a target, Lodge explained.
“The next step is finding a drug that interacts selectively with it,” he said. “And we have some ideas how to do that.”
The study was published in Molecular Psychiatry.