New Research Found That Ketamine, A Drug Known For Inducing Dissociation, Actually “Switches” Neuronal Activity Within The Neocortex
Humans can sometimes experience periods of dissociation– or feeling disconnected from themselves and the world around them.
Despite these feelings being linked to various psychiatric conditions, though, dissociative states can also be prompted following the consumption of both legal and illicit drugs.
And one of the most notable drugs tied to inducing dissociation is ketamine. Ketamine is an anesthetic that is commonly used to medically sedate patients or reduce pain following medical operations.
But, in recent years, countless researchers have also turned to the drug for another application– ketamine’s potential as a treatment option for some forms of depression.
While numerous scientific studies have analyzed ketamine’s therapeutic benefits, not much is known about the neuronal and cellular mechanisms at play which produces the dissociative states.
So, researchers from the University of Pennsylvania recently set out to gain a further understanding of the drug’s processes in a new study.
“As anesthesiologists, we routinely use ketamine for its reliable anesthetizing properties during surgeries. These patients often experience hallucinations, such as a sense of being outside of one’s own body, when they awaken from anesthesia,” explained Joseph Cichon, one of the study’s researchers.
“And from the growing body of work by psychiatrists on ketamine, we know that lower ketamine doses have also been successfully used to treat depression and other related psychiatric conditions.”
In fact, ketamine has even been found to leave lasting therapeutic effects on patients with depression for up to two weeks– even though the drug will only remain within a patient’s system for just one hour following injection.
Yuriy Shevtsov – stock.adobe.com – illustrative purposes only, not the actual person
So, it has become clear that ketamine is a worthwhile treatment avenue to explore, hence why the University of Pennsylvania research team decided to conduct an experiment on mice aimed at analyzing the mechanisms which underpin ketamine-induced dissociative states.
In the experiment, the mice received a dose of ketamine that was anticipated to result in dissociative states.
Then, the researchers observed the animals’ brain activity by utilizing two-photo microscopy– or an imaging technique that enables researchers to continuously analyze specific neurons or individual cells inside an animal’s brain for several minutes or days.
According to Cichon, they also expressed GCaMP6– a fluorescent calcium sensor– in order to image neuronal activity among specific cell types.
“This protein changes its fluorescent intensity depending on the calcium concentration in the neuron, which rises and falls with neuronal firing,” Cichon said.
And by observing the fluorescent signal fluctuations among individual neurons, the researchers were then able to image how ketamine is able to alter the neuronal activity pattern of specific individual neurons.
Then, upon analyzing these neuronal recordings, the researchers ultimately found that ketamine essentially “switched” the cortical activity within the animals’ brains.
In other words, neurons that were previously silent were spontaneously activated; meanwhile, neurons that were highly active suddenly became suppressed.
Of course, interpreting these findings is far from an easy feat– most notably because it is extremely difficult to determine whether or not the mice experienced dissociative states.
Nonetheless, the research team successfully identified two distinct cortical neuron populations. The first is active during wakefulness, then suppressed following ketamine treatment, and the second is typically silent but activated following administration of the drug.
And moving forward, these findings could help open the door for new discoveries regarding the neural processes that result in the brain becoming disconnected from the environment while still having subjective experiences.
Although, Cichon’s team is particularly interested in exploring the common elements present in various drugs, which all produce a dissociative state– such as psychedelic drugs and other anesthetic agents, including Nitrous Oxide (also known as laughing gas).
“We are also extremely interested in determining the relationship between the acute changes in brain activity imposed by these drugs and their long-lasting therapeutic effects, as this may help develop new drugs to treat neuropsychiatric diseases,” Cichon added.
To read the study’s complete findings, which have since been published in Nature Neuroscience, visit the link here.
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