Neuroscientist Prof Jenny Morton has for many years used sheep to try to gain a better understanding of the human brain, and particularly how it goes wrong in Huntington’s disease. Her latest finding, however, may explain some of the side-effects of the drug ketamine.
This current study is as part of a larger research project into Huntington’s disease, seeking to understand why human patients carrying the Huntington’s gene respond differently to various drugs. Sheep were used because they are recognised as a suitable pre-clinical model of disorders of the human nervous system, including Huntington’s disease.
To study the effect of therapeutic drugs on the brains of people living with Huntington’s disease, the researchers used electroencephalography (EEG) to measure immediate changes in the animals’ brain waves once ketamine – an anaesthetic and pain relief drug – was administered.
Low frequency activity dominated while the sheep were asleep. When the drug wore off and the sheep regained consciousness, the researchers were surprised to see the brain activity start switching between high and low frequency oscillations. The bursts of different frequency were irregular at first, but became regular within a few minutes.
“As the sheep came round from the ketamine, their brain activity was really unusual,” Jenny Morton explained. “The timing of the unusual patterns of sheep brain activity corresponded to the time when human users report feeling their brain has disconnected from their body. It’s likely that the brain oscillations caused by the drug may prevent information from the outside world being processed normally,”
Ketamine is widely used as a safe anaesthetic and pain-relief drug for treating large animals including dogs, horses and sheep. It is also used medically, and is known as a ‘dissociative anaesthetic’ because patients can appear awake and move around, but they don’t feel pain or process information normally – many report feeling as though their mind has separated from their body.
At lower doses ketamine has a pain-relieving effect, and its use in adult humans is mainly restricted to field situations such as frontline pain-relief for injured soldiers or victims of road traffic accidents.
Ketamine abusers are known to take doses many times higher than those given to the sheep in this research. It is also likely that progressively higher doses have to be taken to get the same effect. The researchers say that such high doses can cause liver damage, may stop the heart, and be fatal.
Ketamine has recently been proposed as a new treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, very little is known about its effects on brain function.
“We think of anaesthetic drugs as just slowing everything down. That’s what it looks like from the outside: the animals basically go to sleep and are unresponsive, and then they wake up very quickly. But when we looked at the brain activity, it seems to be a much more dynamic process,” said Morton.
This research was funded by CHDI Inc. It was reviewed and approved by the Ethics Committee of the University of Cambridge.
Nicol, A.U. & Morton, A.J. ‘Characteristic patterns of EEG oscillations in sheep (Ovis aries) induced by ketamine may explain the psychotropic effects seen in humans.’ Scientific Reports, June 2020. DOI: 10.1038/s41598-020-66023-8