A widely used anesthetic gives honeybees jet lag, but only if they’re knocked out during the day.
Honeybees, as stand-ins for surgery patients, confirm that a bout of the general anesthetic isoflurane acts directly on the biological clock that governs body rhythms, reports chronobiologist Guy Warman of the University of Auckland in New Zealand. Nighttime anesthesia hits the internal clock at a different phase when the drug effects don’t break the rhythm, he and his colleagues report online April 16 in Proceedings of the National Academy of Sciences.
“Quite novel and notable,” Ravi Allada of the Center for Sleep and Circadian Biology at Northwestern University in Evanston, Ill., says of the new study.
Daily rhythms of body processes matter in medicine, Warman explains. Even so, he doesn’t advise scheduling all surgery at night as a result of the new findings. “Then your anesthetist and your surgeon are exhausted and more likely to make errors,” he says.
Instead, the research has inspired him and his colleagues to start developing ways to keep the clock ticking normally, perhaps by adding light therapy to surgery protocols.
Doctors have seen that people often emerge from general anesthesia disoriented in time and often sleep fitfully for some time afterward. To see whether anesthesia itself causes the effects and whether it does so by acting directly on the underlying master clock, Warman and his colleagues designed experiments using honeybees. Honeybees are great for testing effects on biological clocks, Warman says, because their clock genes are more similar to mammals’ than to other insects studied so far. Also the bees have plenty of well-studied behaviors that depend on the functioning of their built-in molecular clock.
Researchers trained bees to fly out into a field to visit an artificial flower for sugar water. For the test, researchers caught the bees as they buzzed in for a sip and anesthetized them for six hours. When the bees woke up and set off for their hive again, they flew at the wrong angle. Honeybees navigate in part by the position of the sun, and their built-in biological clock lets them correct course for the sun’s movement across the sky during the day. After anesthesia, though, the bees made their “correction” as if the time were hours earlier.
In another test inside the lab with no outdoor cues, daytime anesthesia threw off the usual activity patterns in the hive for the next several days. Also cycles of clock gene activity showed a delay as if reset. But the researchers didn’t see a similar disruption to the bees’ behavior and gene activity after nighttime anesthesia.
What Matthias Eikermann of Massachusetts General Hospital in Boston would like to know is how bees would respond at a variety of dose concentrations of the anesthetic instead of just the one tested. Such information could clarify just what aspects of bee physiology the anesthetic acts upon.
Testing for clock effects in bees was a good start because researchers could control for most of that factors that can confound results in human trials, says neurobiologist Nancy Chamberlin of Beth Israel Deaconess Medical Center in Boston. “The results of this study make the more difficult human studies worth doing to see if there is a clinical relevance or not,” she says.
