Study suggests region of prefrontal cortex impacted by ketamine

June 9, 2015 by Bob Yirka, Medical Xpress report
One 10 ml vial of 1000 mg ketamine. Credit: Psychonaught/Wikipedia

(Medical Xpress)—A team of researchers working at Yale University has found that a region of the brain's prefrontal cortex known as the infralimbic prefrontal cortex (IL-PFC) appears to be the part of the brain involved that reacts to ketamine, causing relief of depression symptoms. In their paper published in Proceedings of the National Academy of Sciences, the team describes how they tested the impact of ketamine on neural activity in the IL-PFC and what they learned in the process.

Ketamine is a well known , partly because it has been used in some instances to successfully treat depression in patients (very quickly) that did not respond to any other medication or treatment, partly because it has hit the underground as a popular illicit drug (due to the hallucinations it can cause), and partly because of its use as a date rape drug. Despite its widespread renown, scientists still do not really understand how it does what it does to the human brain. To learn more, the researchers with this new effort focused on its impact on the IL-PFC, a region of the brain that has in the past been associated with emotional responses.

To better understand what happens when Ketamine is introduced into the brain, the researchers watched neural and behavioral activity as Ketamine was introduced indirectly (via the blood) and directly into rat brains. They found that deactivating neural activity in the IL-PFC prior to administering the drug caused a halt to systematic effects and injecting the drug directly into the IL-PFC caused the systematic effects to come about, suggesting that the IL-PFC is the region of the brain that is most impacted by the drug. The team found also that stimulating the same region optogeneticcally resulted in the same systematic effects as injection of . In addition, the researchers found that use of ketamine caused an increase in the number of synapses in the IL-PFC, suggesting the drug had a long term or even permanent impact on the .

Taken together, the results show, the team suggests, that other alternatives to ketamine for use in treating depression might be found that do not have the harmful side effects. The team plans to continue their research, hoping to better understand how it is that ketamine causes the observed changes in in the IL-PFC.

Explore further: Ketamine found to alleviate depression

More information: Optogenetic stimulation of infralimbic PFC reproduces ketamine's rapid and sustained antidepressant actions, Manabu Fuchikami, PNAS, DOI: 10.1073/pnas.1414728112

Abstract
Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

Related Stories

Ketamine found to alleviate depression

April 10, 2015
Researchers at the University of Hertfordshire have found that Ketamine, which has a reputation as an illicit 'recreational' drug, has an extremely large depression reducing effect. Although Ketamine has been in medical use ...

Ketamine helps see how the brain works in clinical depression

June 16, 2011
(Medical Xpress) -- In a new study published in Nature, Lisa Monteggia from the University of Texas Southwestern Medical Center looks at how the drug ketamine, typically used as an anesthetic or a popular recreational drug ...

Research shows why ketamine is an effective antidepressant but memantine is not

May 27, 2014
(Medical Xpress)—Ketamine is a fast-acting antidepressant. However, it can create symptoms that mimic psychosis. Therefore, doctors don't give it to depressed patients. Memantine, a similar drug, does not have psychotomimetic ...

Researchers look at therapeutic benefits of ketamine

May 1, 2013
The largest trial into the use of Electroconvulsive Therapy (ECT) in the UK in more than 30 years will look into how the use of the Class C drug ketamine might reduce the side effects of ECT for those being treated for severe ...

Scientists explain how ketamine vanquishes depression within hours

October 4, 2012
(Medical Xpress)—Many chronically depressed and treatment-resistant patients experience immediate relief from symptoms after taking small amounts of the drug ketamine. For a decade, scientists have been trying to explain ...

Molecular profiling of Ketamine's rapid antidepressant effect

November 12, 2014
One third of the patients with major depressive disorder suffer from treatment resistance and do not respond to commonly used antidepressants. Ketamine, a drug that works through a different mechanism, improves depressive ...

Recommended for you

Broken shuttle may interfere with learning in major brain disorders

June 22, 2018
Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia, and autism.

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

Scientists discover how brain signals travel to drive language performance

June 21, 2018
Effective verbal communication depends on one's ability to retrieve and select the appropriate words to convey an intended meaning. For many, this process is instinctive, but for someone who has suffered a stroke or another ...

Study on instinctive behaviour elucidates a synaptic mechanism for computing escape decisions

June 21, 2018
How does your brain decide what to do in a threatening situation? A new paper published in Nature describes a mechanism by which the brain classifies the level of a threat and decides when to escape.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.