A Blog Around The Clock

Blogging on Peer-Reviewed Research

If this gets more widely known (and, with this post, I am trying to help it become so), you can just imagine the jokes about the new challenges to the aviation industry and the renewed popularity of the Mile High Club, or the cartoons utilizing the phallic shape of airplanes!

Hamsters on Viagra Have Less Jet Lag, Research Shows (also Viagra helps jet-lagged hamsters, maybe humans, too: study and Viagra ‘improves jet lag’):

Hamsters given Pfizer Inc.’s Viagra adapted more quickly to changes in their internal clocks, scientists said.

Hamsters given sildenafil, the chemical name of the drug sold as Viagra, adapted more easily to altered patterns of light exposure to simulate changes caused by air travel across time zones. Long-haul travel desynchronizes the body’s alignment to the day-night cycle, leading to the disorientation of jet lag.

————snip—————-

The researchers synchronized the hamsters to a 24-hour day by simulating light-dark cycles. Once the hamsters adjusted to a cycle, they shifted the light-dark phases forward six hours. One group of hamsters was given saline; the other was given Viagra. The hamsters given Viagra got used to the change 4 days faster, on average, than their counterparts given a placebo. Viagra eased the transition that mimicked crossing the international dateline from west to east, known as phase advancing, and had no effect on a transition that mimicked westward travel.

There should be a rule in journalism making sure that no article about Viagra ever contains the words “harder” and “screw”, especially close to each other. Oooops!

“All animals, including humans, have a harder time with phase advancing,” said Colwell in a telephone interview today. “Humans are unique in our ability to screw up our timing system — you know, jet lag, shift work, staying up too late playing video games, or whatever.”

OK, now seriously…what does the study say?

Given low doses of Viagra (too low to elicit erections in hamsters, but you have to read the article to the end to find that out), the activity rhythms phase-advanced by 6 hours (to the new time-zone) much faster than in the control animals. What does that mean regarding jet-lag? Short-answer: we don’t know. Insufficient information.

Jet-lag is not the product of our desynchrony from the outside world, i.e., not gettig up on time for breakfast after landing in Paris. It is the product of internal desynchrony between our many peripheral clocks. The activity rhythms measured in this study are a good marker for where the pacemaker in the SCN (suprachiasmatic nucleus) is in time, but gives no information about the phase of clocks in other tissues.

The SCN pacemaker is phase-shifted by light. In mammals in general, the response is slow and gradual, with transients seen over several days. This can also be deduced from the shape and size of the Phase-Response Curve seen in most mammals.

The peripheral clocks located in all other tissues are blind to light. They are entrained by the signals from the SCN (or indirectly elicited by the SCN) such as cortisol, melatonin, etc.

So, if you fly from NYC to Paris, it may take your SCN a week to re-entrain to the new time-zone, but it may take two weeks for the clocks in muscles or lungs for instance, and several weeks for the clocks in the liver and intestine to reset to the new time. During that period, the organs and organ-systems that are supposed to work together are out of sync with each other and, as a result, you feel sick (and if you do this to yourself very frequently – you WILL get really sick).

The question that comes to my mind after reading about this study (warning: I have not yet received a copy of the actual paper, but the author is interviewed in the article and I assume that what follows is correct – send me the paper and I’ll check) is this:

a) Will speeding up of resetting of the SCN by Viagra also speed-up the resetting of the peripheral clocks?

b) Or, will peripheral clocks take their usual time to reset anyway?

c) Or, if shifting the SCN so fast will place its signals on the wrong portion of the peripheral clocks’ Phase-Response Curve and actually slow down the resetting of the clocks in liver, kidneys, etc., thus making the internal desynchrony (jet-lag) even more pronounced and long-lasting?

We don’t know! Somebody should do the experiment in which rodents given Viagra (in comparison to controls, of course) are monitored for a variety of their rhythms driven by various peripheral clocks or even directly measuring the phase of peripheral clocks using luciferase-tagged clock-genes. I would not start with human trials before such an experiment is performed as Viagra can potentially (option c above) make it MORE difficult to deal with jet-lag.

Comments

  1. #1 coturnix
    May 22, 2007

    I have now read the paper. It is interesitng and not bad at all, but there is nothing in the post I’d change: the findings really do not address jet-lag at all.

  2. #2 Stagyar zil Doggo
    October 7, 2007

    Coturnix,
    What about people with non-24 hour sleep wake syndrome? Do you think Sildenafil could be useful to them? (Insert blind cane joke here.) Since they need to advance their clocks a small amount every day (I would guess around an hour) instead of several hours all at once like the jetlagged, perhaps your point c) above would not apply?

    Lastly, is there any reason to apriori exclude the possibility that Sildenafil acts directly on at least some peripheral clocks? Do peripheral clocks not use cyclic-GMP?

    Wait wait! (Sorry, the questions keep coming the more I think about this.) Is there good reason to think that the observed effect is not phase dependent? I.e. could the Sildenafil phase response curve be other than flat?

    regards,

    PS: In a twist of irony, scienceblogs won’t let me use the V-word while commenting on an article about the V-word.

  3. #3 coturnix
    October 7, 2007

    All excellent questions! No data on any of this yet, of course, but all are plausible. For incremental daily shifts Sildenafil may be useful, but we don’t know yet. It is certainly possible that peripheral clocks may respond to it, but we don’t know yet. And I’ll bet you a dollar that the PRC to Sildenafil is not flat, but, now I am getting boring, we don’t know yet.

    I am sure that this paper will stimulate (not in that way!) further hard research ;-)

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.