Blame It On Adenosine

What is the main action of caffeine?  To block adenosine receptors – in the brain and the rest of the body.

And what does adenosine do?

Tell us that we’re getting sleepy.  And foul up our memories.

So does blocking adenosine through caffeine improve memory?

If only life were so simple.

Where Sleep Starts

Cliff Saper, chair of Neurology at Harvard, has been among many arguing that a specific, small area of the brain, the ventrolateral preoptic region, is where the process of  sleep generally begins. Sleep appears to start when adenosine levels rise.

Adenosine is part of some of the major energy chemicals in your body – particularly adenosine triphosphate – better known as ATP.

Use more energy- as in staying awake – and more adenosine accumulates.  As it accumulates, you feel tired, fatigued, and sleepy.

And blocking adenosine receptors, as in squirting caffeine into the brain, does keep us and other animals awake.

Could it also impact sleep’s affect on memory?  Was it direct sleep loss or more the level of brain adenosine that worsens memory performance?

That’s when we come to Ted Abel’s mice  at the University of Pennsylvania.

   A Different Breed of Mice

Some mice bred at the University of Pennsylvania were very different from your normal variety.

One group had been genetically engineered to lack adenosine receptors.  Adenosine could not work, because the lock-in-key receptor necessary to make those effects turn on had been genetically deleted.

The other mice were engineered to lack the effects of adenosine not genetically but electronically – with special pumps that constantly stopped the adenosine receptors from working.

Then, fortunately, there were normal mice for comparison.

When the normal mice were kept up very late, they became worse and worse at memory recognition tasks.

When the adenosine blocked mice were kept up late, their memory performance did not decline through the night.

No sleep for these mice – but memory preserved. In some ways, it was as if they did not know they were sleep deprived, as Abel put it.

So adenosine seems part of the process that can worsen memory.   And adenosine is also produced in greater and greater amounts the longer that we’re up and awake.

If adenosine is blocking memory, can’t we use caffeine to ride to the rescue and make us think and perform better?

The Unfulfilled Promise of Caffeine

There are studies, particularly in animals, that show short term advantages to caffeine use in improving memory.  However, that’s not close to the whole story:

Prolonged use of caffeine in animal studies appears to decrease brain cell growth in the hippocampus – a major memory area.

High caffeine use in humans leads very quickly to tolerance – the body produces more adenosine receptors to make up for those blocked by caffeine. More caffeine tolerance means that adding caffeine to the mix won’t work – you can add and add caffeine, but the system now has so many receptors it can more or less ignore it.

Caffeine also hits other receptors in the body – including  inside the heart – which can lead to heart irritability.

More caffeine also can make people nervous, irritable, and nauseous – one reason caffeine is used in panic research  studies to induce panic attacks – which it does quite well.

Caffeine tolerance also eventually creates caffeine withdrawal, with potential irritability, crankiness, nervousness, diarrhea, panic attacks, racing heart, as well as overpowering fatigue and lassitude.

Which means there are reasons to be wary of highly caffeinated energy beverages – which frequently  change the moods of the young people to whom they are marketed.

It’s also an argument for getting one’s dose of caffeine from time tested beverages like coffee and tea – which also provide many other substances and anti-oxidants that may help prevent tumors and diabetes – as well as sustain enjoyable social encounters.

Bottom Line

We can’t change human nature – at least not yet.  The longer we’re up the more adenosine we produce.  Past a certain level, we not only get sleepy but our memory and cognitive performance declines.

We really do need our rest.  And even if we were genetically bred to lack adenosine receptors, we would still need to rest.

For rest is regeneration.  All that accumulated  adenosine marks the passage of time during which our cells have used up food and materials to remake themselves.

And all those cells have to be replenished and restored – and then given the time they need to regenerate.

Regeneration is what rest is all about.
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