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Transcript
LESSON 4.4 WORKBOOK Can caffeine treat narcolepsy? DEFINITIONS OF TERMS Adenosine – neurotransmitter that accumulates in the brain during wakefulness, implicated as an important ‘sleepiness’ factor. For a complete list of defined terms, see the Glossary. Remember that sleepiness is controlled by two factors: length of time our brains have been awake and active, and the time of day. Let’s turn our attention now to the first factor – the length of time we’ve been awake and active. Adenosine The longer we stay awake, the sleepier we become and the pressure to sleep is hard to resist. Why? What is responsible for the sleepiness that increases the longer we’re awake and mentally active? The precise mechanism is unknown but it seems that the neurotransmitter adenosine is an important ‘sleepiness’ factor (Figure 19). Researchers measured the levels of adenosine in the basal forebrain of cats during 6 hours of prolonged waking and during 3 hours of sleep afterwards. They found that adenosine levels rise during wakefulness and slowly decrease during sleep. They concluded that the accumulation of adenosine that occurs after we have been awake for a long period may be the most important cause of the sleepiness that follows periods of wakefulness (Figure 20). Adenosine Wo r k b o o k Lesson 4.4 Figure 19: Adenosine, the ‘sleepiness’ factor, is released by neurons and glial cells. Figure 20: Adenosine in the forebrain region of cats during 6 hours of waking followed by 3 hours of recovery (sleep). Levels of adenosine rise during wakefulness and slowly decrease during sleep. What is adenosine? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ What happens to adenosine levels during wakefulness? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ 118 LESSON READING Another clue about adenosine’s role in promoting sleep came from studying caffeine, which as we all know, decreases drowsiness and promotes wakefulness. Caffeine Caffeine Caffeine is found in coffee, tea, cocoa beans, and other plants. It is a drug that produces excitatory effects (Figure 21). In much of the world, a majority of the adult population ingests caffeine every day – fortunately, without apparent harm. Several studies have shown that caffeine prevents the normal drowsiness that occurs after being awake by binding to and interfering with the receptors that recognize adenosine. One study in particular used mice that didn’t have any adenosine receptors. When these mice where given caffeine, it failed to keep them awake, unlike mice with adenosine receptors, showing that indeed you need adenosine receptors for caffeine to have its normal effect. Figure 21: Caffeine molecular structure is similar to adenosine, so it can bind to adenosine receptors and also promote wakefulness. There is now overwhelming evidence that caffeine’s effect as a stimulant occurs because it binds to adenosine receptors and blocks the action of adenosine (Figure 22). You can see now why that first cup of coffee in the morning helps shake off the lingering sleepiness of the previous night, how a midafternoon coffee break helps bring you back to an alert state during a post-lunch period of drowsiness, or how that late night cup of coffee keeps you awake (unless you’ve already built up a tolerance to caffeine). A. Adenosine binds to its receptors. When levels are high enough, it promotes sleep Wo r k b o o k Lesson 4.4 B. Caffeine also binds to adenosine receptors and stops adenosine binding. Sleep is prevented Figure 22: Adenosine signaling. (A) When adenosine levels are high they bind to adenosine receptors and cause us to fall asleep. (B) Caffeine also binds to the adenosine receptors, which stops adenosine from binding. By preventing adenosine from binding to its receptors, caffeine keeps us awake. How much caffeine do you drink in an average day? When do you have it? Do you recognize any effects it’s having? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ How does caffeine keep us awake? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ 119 LESSON READING Let’s take a minute now to introduce the concepts of tolerance and withdrawal – two topics we’ll spend a lot more time talking about in Chapter 5. The concepts may make more sense in the context of a drug that probably everyone has used — caffeine. We can define a drug as a chemical that changes behavior. So caffeine is a drug, but it does not produce the compulsive drug-seeking behavior that people who abuse amphetamine, cocaine or other opiates show. Therefore, it poses minimal risk and is not controlled by government laws and regulations – so it’s readily available, and legal, to consume. Now, let’s look at tolerance and withdrawal with caffeine, our most popular drug. DEFINITIONS OF TERMS Tolerance – decreased response to a drug as a direct result of repeated drug exposure. Withdrawal – the condition brought on by the elimination from the body of a drug on which the person has become physically dependent. For a complete list of defined terms, see the Glossary. Tolerance is what happens when we are repeatedly exposed to a drug – we become less susceptible to its effects. Prolonged use of caffeine does lead to a moderate amount of tolerance. Tolerance explains why those of us who consume caffeine regularly do not experience the same stimulating effects as nonusers, and why those of us who regularly use caffeine need more of the it to get the same effects. Withdrawal is what happens if we try to stop using a drug we’ve become dependent on. People who suddenly stop taking caffeine often complain of headaches, drowsiness and difficulty concentrating. These withdrawal symptoms will stop after consuming more caffeine, but if the person continues to abstain, they’ll disappear within a few days. Often, especially with drugs of abuse, these withdrawal symptoms are so severe that individuals continue to consume the drug simply to avoid the withdrawal symptoms. Could caffeine be used to treat narcolepsy? If caffeine is a stimulant that keeps us awake, could it be used to treat narcolepsy – a disorder characterized by falling asleep at inappropriate times? Although, some patients with mild narcolepsy do report that caffeine helps them overcome their daytime fatigue, caffeine is not currently an approved treatment because it is not strong enough to override the defects in orexin signaling that cause narcolepsy. But, luckily other drugs have been developed that do. Not surprisingly one drug, modafinil, which has been used to treat narcolepsy, is thought to act on orexin neurons. Researchers found that giving modafinil increased orexin neuron activity, but whether this is a direct or indirect effect is still not clear. Other drugs used to treat narcolepsy include central nervous system stimulants and antidepressants that are much stronger than caffeine. The sleep attacks can be reduced by stimulants such as methylphenidate (Ritalin). The untimely episodes of REM sleep can be helped by antidepressant drugs. Wo r k b o o k Lesson 4.4 What is tolerance? How would you know if you’ve developed tolerance to a drug? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ What is withdrawal? How would you know if you’re experiencing withdrawal symptoms? ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ 120 STUDENT RESPONSES Would caffeine be an adequate treatment for narcolepsy? Why or why not? ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ Remember to identify your sources ______________________________________________________________________________________________________ As caffeine wears off, we feel incredibly sleepy – why is that? What has happened to our adenosine levels after we consume caffeine? ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ Wo r k b o o k Lesson 4.4 ______________________________________________________________________________________________________ 121
